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Effect of homocysteine on pregnancy: A systematic review
Abstract
Research purpose was to put together the available pieces of present scientific data and to close the gap in the knowledge of Hcy levels in pregnancy and its association with some pregnancy complications. Scientific data were taken from research papers published between January 1990 and December 2017, and found on the Internet (PubMed, ClinicalKey and Embase databases) by the following tags entered in English, Russian, French and German languages: pregnancy, homocysteine, pregnancy complications, pregnancy loss, preeclampsia, intrauterine growth restriction, and placental abruption. The review showed that Hcy levels range in uncomplicated pregnancy. Upon that, Hcy level tends to decrease during the second and third trimesters. Some studies have revealed a link between polymorphism and abortion. Sufficient data were obtained indicating the relationship between HHcy and PE. Placental abruption was also associated with high Hcy levels increasing the risk 5.3-fold, but still there are data not supporting the hypothesis that Hcy levels correlate with placental abruption.
... We did not find differences between periods patients Vitamin B12 is essential for hematological and neurological processes and serves as a cofactor in 2 enzymatic reactions: 1) conversion of methylmalonyl-CoA to succinyl-CoA; 2) remethylation of homocysteine to methionine (Met). In vitamin B12 deficiency, methylmalonyl-CoA is converted to methylmalonic acid (MMA) (Prick et al., 2012;Gaiday et al., 2018). Consequently, in B12 deficiency, total Hcy (tHcy) and methylmalonic acid (MMA) increase in plasma and, thus, are important functional biomarkers of vitamin B12 status (Vugteveen et al., 2011). ...
... Therefore, Phe levels < 360 μmol/L prior to conception and throughout pregnancy are recommended (Rouse and Azen, 2004;Prick et al., 2012). In general, pregnant women with low levels of vitamin B12 and folate and/or high Hcy levels are at higher risk of pregnancy complications, such as neural tube defects, recurrent pregnancy loss, preeclampsia, prematurity, and poor birth outcomes (Nelen, 2001;Gaiday et al., 2018). Plasma tHcy is usually lower during the first two trimesters of pregnancy and returns to preconception concentrations during late pregnancy (Murphy et al., 2004). ...
... THcy levels were especially high in our PKU patients before pregnancy (mean 22 μmol/L). During pregnancy, tHcy levels were within normal range, similar to those described in healthy pregnant women (Murphy et al., 2002;Gaiday et al., 2018). ...
Hyperhomocysteinemia and vitamin B12 deficiency have been reported in patients with phenylketonuria. In this study, total homocysteine (tHcy) and methylmalonic acid (MMA) levels were analyzed in samples from 25 phenylketonuria (PKU) patients. Comparisons were made between pre- and post-treatment values (n= 3); on treatment values, between periods with high and normal/low phenylalanine (Phe) levels (n= 20); and in women before, during and after pregnancy (n= 3). THcy levels decreased after treating PKU with metabolic formula (p=0.014). Except for a pregnant woman before pregnancy, none of the patients had tHcy values above the normal range. In fact, tHcy was < 5 μmol/L in 34% of the samples. We observed a decrease in Phe, tHcy, and tyrosine levels during pregnancy. MMA levels did not differ significantly, with values remaining in the normal range. These data indicate that there was no B12 deficiency in patients who adhere to the diet. In conclusion, in PKU patients treated with metabolic formula, tHcy is frequently not elevated, remaining even in the lower normal range in some patients. Thus, clinical follow-up and adherence to dietary treatment are crucial to prevent B12 deficiency.
... High plasma homocysteine levels have been proven to serve as a risk factor for multiple conditions such as atherosclerosis, coronary artery disease, essential hypertension, retinal vein occlusion, venous thromboembolism, cancers, infertility, and pregnancy complications (preeclampsia, recurrent pregnancy loss, etc.) [14,27,29,33,[52][53][54]. Hyperhomocysteinemia has been reported in 40% of patients with coronary artery disease, and cerebral or peripheral artery disease [15,53]. ...
... The MTHFR C677T polymorphism results in low enzymatic activity and an accumulation of homocysteine [87]. Hyperhomocysteinemia leads to thrombotic events in a vascular bed of various localizations, including the placenta, causing severe conditions (Figure 3) [14,27,29,33,[52][53][54]. ...
... Future research directions may also be highlighted. Increased blood levels of homocysteine during pregnancy are associated with multiple pregnancy complications, including preeclampsia, spontaneous abortions, IUGR, and placental abruption [54,[88][89][90]. Moreover, elevated plasma homocysteine has been proposed to be an independent risk factor for preeclampsia [88][89][90]. ...
The rationale and importance of folic acid supplementation during pregnancy for fetal congenital defect prevention are accepted worldwide. Moreover, a sufficient plasma concentration of folates can reduce the incidence of spontaneous abortions, and support the normal expansion of placental blood vessels, ensuring physiological placental blood flow, thus promoting appropriate fetal growth and development. Furthermore, there is emerging evidence that long-term supplementation with folic acid can effectively prevent preeclampsia. Preeclampsia is unique to the human species in complications during pregnancy, which contributes to maternal and perinatal mortality worldwide. In the pathogenesis of preeclampsia abnormal placental invasion, the excess of antiangiogenic factors and maternal–placental syndrome play a key role. Increased blood levels of homocysteine during pregnancy are associated with the risk of preeclampsia. Moreover, hyperhomocysteinemia has been proposed to be an independent risk factor for preeclampsia. Folate supplementation helps to decrease elevated levels of homocysteine; thus, the role of folic acid supplementation in pregnancy is even more important. Multiple reports suggest that folate administration decreases the level of serum homocysteine and, therefore, reduce the risk and severity of preeclampsia. However, the association between folic acid supplementation and the decreased risk of preeclampsia has been investigated with controversial conclusions. Currently, the optimal dose of folic acid that is effective for preeclampsia prevention remains uncertain. In this review, we aim to summarize the accumulated knowledge on the role of folic acid in the pathogenesis of preeclampsia, and the possible impact of folate supplementation on the decreased risk of preeclampsia.
... Yapılan çalışmalarda, hiperhomosisteinemi'nin kardiyovasküler, serebral, vasküler, renal bozukluklar gibi pek çok hastalıkta rol oynadığı gösterilmiştir (5,6). Tekrarlayan gebelik kayıplarında homosistein düzeylerinin arttığını ya da değişmediğini gösteren çalışmalar mevcuttur (7,8). ...
... Uterusta anatomik bozukluklar, parenteral karyotip olumsuzlukları, antifosfolipid antikorlar, endokrin, immün, trombofilik bozukluklar, anne yaşı, obezite bunlardan bazılarıdır (23). Bu nedenlerden biriside homosistein düzeylerinin artışı olarak gösterilmektedir (7). Homosistein metiyoninden oluşan, transsülfirasyonla B6 vitamini varlığında sistatyonin beta sentaz enzimi ile önce sistationine sonrasında sisteine ya da remetilasyonla B12 vitamini ve metilen tetrahidrofo-lat redüktaz (MTHFR) enzimi ile oluşturulan folik asitin bir formu olan N5 metil tetrahidrofolik asit varlığında metiyonin sentaz enzimi varlığında tekrar metiyonine dönüşerek metabolize olan bir aminoasittir (24,25). ...
... Başka bir çalışmada ise homosistein düzeyleri yüksek olan gebelerin, düşük materyalinin incelenmesinde, koryonik vasküler sisteminin yeterince gelişmediği ve defekt olduğu bulunmuştur (29). Tekrarlayan gebelik kayıplarında homosistein düzeylerinin yüksek olduğu ya da değişmediği gösterilmiştir (7,8). ...
Tekrarlayan gebelik kaybı iki veya daha fazla başarısız klinik gebelik veya intrauterin olması gerekmeyen ardışık üç gebelik kaybı olarak tanımlanır(3). Tekrarlayan gebelik kayıplarında homosistein düzeylerinin arttığını yada değişmediğini gösteren çalışmalar mevcuttur. Bu çalışmada, tekrarlayan gebelik kayıplarında serbest radikal benzeri etki gösteren homosistein ve homosisitein’in atılımında önemli fonksiyonlara sahip olan B12 ve folik asit düzeylerinde değişim olup olmadığı amaçlandı. Gereç ve Yöntem: Bu çalışma, Kahramanmaraş Necip Fazıl Şehir Hastanesi Kadın Doğum ve Çocuk Hastalıkları ek binasında, retrospektif olarak ocak ve aralık 2020 tarihleri arasında 1. trimester tekrarlayan gebelik kaybı nedeniyle başvuran, 30 tekrarlayan gebelik kaybı olan hasta (Grup I) ve 1. trimesterde bulunan herhangi bir şikayeti olmayan 30 sağlıklı gebede (Grup II) plazma homosistein, serum folik asit ve vitamin B12 düzeyleri değerlendirildi. Bulgular: Homosistein düzeyleri (µmol/L), Grup I: 17,6 ± 9,5, Grup II: 11,8 ± 4,6, Vitamin B12 düzeyleri (ng/L): Grup I: 233,4 ± 69,5, Grup II: 262,4 ± 76,7, folik asit düzeyleri (µg/L): Grup I: 7,7 ± 3,3, Grup II: 11,3 ± 3,7 olarak saptandı. Homosistein düzeylerinde; tekrarlayan gebelik kaybı olan grupta (Grup I) istatistiksel olarak anlamlı yükseklik saptandı (p<0.05). Folik asit düzeylerinde; tekrarlayan gebelik kaybı olan grupta (Grup I) istatistiksel olarak anlamlı düşüklük bulundu (p<0.05). Vitamin B12 düzeylerinde gruplar arasında istatistiksel olarak anlamlı bir fark görülmedi (p=.0.186). Yaşlar arasında istatistiksel olarak anlamlı bir fark saptanmadı (p=0.210). Sonuç: Tekrarlayan gebelik kaybı olan hastalarda, homosistein, vitamin B12, folik asit düzeylerinin ethiolojide önemli bir etken olduğunu düşünmekteyiz
... Balanced Hcy remethylation and trans-sulfuration are critical metabolic pathways because Hcy is a vascular toxin which may cause endothelial injury at various organs [8]. Hyperhomocysteinemia and Hcy related pathway disorders are one of the critical factors behind obstetrical complications and thrombotic events [9]. MTHFR polymorphisms with impaired Hcy metabolism disorders are potential risk factors for placental inflammation and impaired foetal perfusion which leads to maternal complications and a key reason for increased incidence of congenital abnormalities and foetal aneuploidies [1,2,10]. ...
... The same study also reported that T allele and TT genotype frequencies among 1,000 heathy north Indian individuals were 11% and 1% respectively [15]. Several studies revealed that the elevated Hcy levels due to these polymorphisms during pregnancy were associated with many adverse maternal outcomes (AMO) like pre-eclampsia, miscarriage, recurrent pregnancy loss, placental abruption, pre term delivery and intrauterine growth restriction (IUGR) [2,9,10,[16][17][18][19] congenital malformations [20][21][22] and autism spectrum disorder [23]. ...
... Based on the previous studies, we postulate that the disrupted homocysteine metabolism with MTHFR polymorphism could be the reason for these pregnancy complications [2,9,22]. However, larger studies with a higher sample size are needed to confirm this and establish a causal association. ...
Objectives
To determine the occurrence of MTHFR gene polymorphisms and to study their association with vitamin B12 deficiency and adverse perinatal outcomes among a cohort of pregnant women from Kaniyambadi block, Tamil Nadu.
Methods
120 consecutive pregnant women who were ≤20 weeks of gestational age from the 82 villages of Kaniyambadi block were recruited. Genomic DNA was isolated from the peripheral blood. PCR amplification was done followed by Sangers sequencing. Maternal and neonatal outcomes were extracted. Data was entered and analysed.
Results
Our study found the occurrence of c.1298A>C variant in homozygous state in 14.2% and c.677C>T heterozygous state in 15%. Sanger sequencing of exon 7 identified another pathogenic variant c.1262G>T in heterozygous state in two of them. Both the mothers who harboured that variant had preterm delivery and one of them gave birth to a low-birth-weight neonate. In the entire cohort, 5% of the mothers had abortion, 4.2% of them had preterm delivery and 8.8% of the neonates had low birth weight. Presence of c.1298A>C or c.677C>T variants were associated with vitamin B12 deficiency [Pearson Chi squared value (x ² )=7.9 and 7.6 respectively; p=0.02]. Heterozygous pathogenic variant c.1262G>T was associated with both adverse maternal [x ² =11.5; p=0.001] and neonatal [x ² =18.3; p=0.009] outcomes.
Conclusions
MTHFR gene polymorphisms could be associated with several adverse perinatal outcomes and vitamin B12 deficiency. Further larger studies are needed to prove the pathogenicity of c.1262G>T variant on pregnancy.
... In a study conducted by Gaiday et al. [14], the majority of the population had a mean gestational age of 12 weeks, and Chamotra et al. involved women with 20 weeks of gestation as the study population, whereas in the current study, among both groups, the majority of females had a gestational age of 10 weeks [12]. In a study by Mascarenhas et al., there was no statistical correlation between other associated factors and placenta-mediated complications [15]. ...
... Whereas, in a study given by Noori et al., the mean SBP was 155.6, and the mean DBP was 113.3 [16]. Additionally, among high and normal homocysteine level groups, the majority of women delivered after 38 weeks, which correlates well with the study given by Gaidey et al., in which the majority delivered after 38 weeks [14]. ...
Background Placenta-mediated complications, such as preeclampsia, placental abruption, and fetal growth restriction, can indeed lead to significant maternal and perinatal morbidity and mortality. Early detection and management of these conditions are crucial to ensuring optimal outcomes for both the mother and baby. However, there have been inconsistent correlations found between maternal homocysteine levels and placenta-related problems in various studies. Therefore, prospective research based on data pointing to a role for hyperhomocysteinemia in placenta-mediated complications will open doors for early detection and management of these complications. Thus, this study aims to determine if a higher risk of placenta-mediated problems is connected with a higher maternal plasma homocysteine content between 10 and 14 weeks of gestation. Methodology An observational prospective cohort study was conducted in the Department of Obstetrics and Gynecology, consisting of all the antenatal women between 10 and 14 weeks of gestation attending outpatient departments or inpatients admitted in labor rooms or wards having singleton pregnancies. Along with socio-demographic information and detailed history, a clinical examination was performed, and blood samples were collected to determine plasma homocysteine levels. Results As per the receiver operating characteristic curve (ROC curve), the cut-off value taken was <5 for the low level of serum homocysteine, 5 to 15 micromol/L for the normal value, and >15 micromol/L for a raised serum homocysteine level. The cutoff value for our study was 45 micromol/L with a sensitivity of 78.33%, a specificity of 91.67%, a positive predictive value of 90.38%, and a negative predictive value of 80.88% with a diagnostic accuracy of 85%. This means that, for most of the women included in the present study, those who developed placenta-mediated complications had serum blood homocysteine levels of 45 micromol/L or more at 10-14 weeks of gestation. Conclusion Women with high homocysteine levels in the late first trimester had more placenta-mediated complications, such as abruption, pre-eclampsia, restricted fetal growth, and recurrent pregnancy losses, compared to women with a normal level of homocysteine in the late first trimester. Therefore, measuring blood homocysteine levels in pregnancy may be helpful as a diagnostic test for the early detection of high-risk individuals for placenta-mediated complications.
... The results of the study presented in Table (3-1) showed a significant increase in the level of homocysteine in aborted women compared with healthy subjects (pregnant and non-pregnant) with a probability level P≤0.05. Letters: a, b, and c mean that there are significant differences at the probability level P 0.05 When a comparison between the age groups of the study group is made to the level of HCY, the study showed that there is a significant difference at a probability level of 0.05 in its level for the same age group between groups of aborted, pregnant and non-pregnant women, as Figure (3-1) shows that the group (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) years is significantly different from The same category among the studied groups (miscarriages, pregnant and non-pregnant women), as well as the case for the second age group (26-47) years, as high HCY was observed in the miscarriages, pregnant and non-pregnant women of the second category. When a comparison is made between the two age groups of the same group, it is found that the level of HCY is higher in women who have aborted women than pregnant and non-pregnant women, and also in pregnant women compared to non-pregnant women ...
... High HCY in a pregnant woman is a danger to the mother and the fetus, but these risks can be easily prevented by obtaining adequate amounts of folate and vitamin B 6 , B 12 , Zn, and Mg, as the increase is caused by a deficiency of vitamins B 6 , B 12 and folic acid, and it leads to serious growth disorders. It develops into preeclampsia, impaired blood circulation in the placenta, and lack of oxygen inside the uterus, which ends with the end of pregnancy, the occurrence of miscarriage, the death of the fetus, or complications during childbirth, and children are born with low weight or premature birth (24). Some women complain of high HCY, especially those with the MTHFR gene mutation, which may cause abnormalities in the fetus. ...
Homo cysteine is an amino acid that contains sulfur, which is (2_amino_4_ mercaptobiotanic), which is derived from the metabolism of methionine as an essential acid that is metabolized by the methylation pathway, or the transport of sulfur, and any defect in these two pathways leads to an increase in the level of homocysteine in the blood. The aim of the study was to assess the level of homocysteine in women who had miscarriages compared to pregnant and non-pregnant women. The study included (92) samples of women whose ages ranged between (15-47) years and consisted of (31) samples of women with abortion. The patients were compared with (31) samples from pregnant women (30) samples from Unmarried and pregnant women as a control group. Samples were obtained. Blood from the reviews in Salah El-Din General Hospital. The groups of aborted, pregnant and non-pregnant women were divided into two age groups, the first from (15-25) and the second category (26-47). The relationship between the group of miscarriages and the group of pregnant women and non-pregnant women was studied by studying the variables that include the concentration of homocysteine and vitamin D, and the results showed a significant increase in the abortion patients with a probability level P≤0.05 in the concentration of homocysteine when compared with pregnant and non-pregnant women in addition to the increase in the concentration of homocysteine. With age in women who have abortions than pregnant and non-pregnant women. In the study sample, it was also found that there was a significant decrease in the level of vitamin D in the blood of miscarried women as well as pregnant women compared to non-pregnant women at a level of P 0.01.
... Hyperhomocysteinemia results in endothelial damage, it increases the oxidative stress related to PE. 8 Previous studies have examined whether hyperhomocysteinemia in pregnancy is related to adverse outcomes, such as small size for gestational age at birth, PE, recurrent abortions, low birth weight and intrauterine growth restriction. 4,9 Among our patients with PE, homocysteine concentrations gradually and significantly increased throughout the pregnancy, these results are consistent with previously reported findings in Spain and India populations. 10,11 Hyperhomocysteinemia increases the oxidative stress and collagen accumulation that leads to vascular fibrosis, and results in endothelial damage, 9,12 which is a non-protein amino acid that is formed after cleavage of the terminal methyl group from methionine, genetic polymorphism of the enzyme methylenetetrahydrofolate reductase (MTHFR), which catalyses the conversion of 5,10-methylene THF to 5-methyl THF in the folate cycle, also increases homocysteine. ...
... 4,9 Among our patients with PE, homocysteine concentrations gradually and significantly increased throughout the pregnancy, these results are consistent with previously reported findings in Spain and India populations. 10,11 Hyperhomocysteinemia increases the oxidative stress and collagen accumulation that leads to vascular fibrosis, and results in endothelial damage, 9,12 which is a non-protein amino acid that is formed after cleavage of the terminal methyl group from methionine, genetic polymorphism of the enzyme methylenetetrahydrofolate reductase (MTHFR), which catalyses the conversion of 5,10-methylene THF to 5-methyl THF in the folate cycle, also increases homocysteine. 13,14 A study of Turkey revealed homocysteine levels were not correlated with disease severity, 7 but another study in Shanghai showed homocysteine in severe PE were significantly higher than those in the median. ...
Introduction
This study evaluated whether changes in homocysteine concentrations in pregnant women with preeclampsia (PE) might be useful for predicting foetal death.
Materials and methods
This study evaluated 1,368 PE women at two Chinese centres. Medical records were reviewed to collect data regarding maternal age, homocysteine concentrations and other clinical parameters.
Results
Maternal serum homocysteine concentrations were significantly higher in the group with PE than control. Significant differences (p < 0.05) were also observed between the foetal death and survival groups in terms of body mass index, neonatal weight, previous deliveries, gestation length and adverse pregnancy history. Multivariate logistic regression analysis revealed that upper‐quartile homocysteine concentration was a significant risk factor of foetal death in the group with PE, and overall survival rate of patients with high homocysteine concentrations during pregnancy was significantly lower than those with low level (p < 0.05).
Conclusions
Our results indicate that foetal death was associated with upper‐quartile homocysteine concentrations in the group with PE, it can be an indicator of foetal death throughout the pregnancy.
... 8,9 Hence, hyperhomocysteine during pregnancy was associated with recurrent pregnancy loss, preeclampsia, and placental abruption. [10][11][12] The human MTHFR gene contains 11 exons located on the short arm of chromosome 1p36.3. The gene encodes for methylenetetrahydrofolate reductase (MTHFR) that catalyzes the irreversible conversion of 5,10methylenetetrahydrofolate to 5-methyltetrahydrofolate. ...
Objective: To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of homo-cysteine metabolism-related genes in women. Materials and Methods: A case-control study included 90 women with two or more consecutive unexplained pregnancy losses and 92 controlled women without miscarriage history; the female participants were in the age category of 18-35 years. The high-resolution melting technique was used to detect the single-nucleotide variants related to homocysteine metabolism disorder, namely MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphism. Results: The MTHFR C677T polymorphism had significantly correlation with URPL. Indeed, the frequency of the677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group (p < 0.05). However, the allele, as well as genotype distribution of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms showed no significant difference (p > 0.05). MTHFR 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR 9.0; 95% CI, 2.25-35.99; p = 0.001), while the risk increased 10.0-fold (OR 10.0; 95% CI, 1.8-55.53; p = 0.008) when participants had more than the 3 variant loci. Conclusion: The MTHFR C677T polymorphism was a risk factor for URPL, and determining the MTHFR C677T polymorphism had a potential prediction of URPL risk. Moreover, the MTHFR C677T and MTHFR A1298C joint mutants might have a synergistic effect on URPL. Conversely, there is a lack of evidence suggesting the URPL risk of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms.
... 8,9 Hence, hyperhomocysteine during pregnancy was associated with recurrent pregnancy loss, preeclampsia, and placental abruption. [10][11][12] The human MTHFR gene contains 11 exons located on the short arm of chromosome 1p36.3. The gene encodes for methylenetetrahydrofolate reductase (MTHFR) that catalyzes the irreversible conversion of 5,10methylenetetrahydrofolate to 5-methyltetrahydrofolate. ...
Objective: To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of homo-cysteine metabolism-related genes in women. Materials and Methods: A case-control study included 90 women with two or more consecutive unexplained pregnancy losses and 92 controlled women without miscarriage history; the female participants were in the age category of 18-35 years. The high-resolution melting technique was used to detect the single-nucleotide variants related to homocysteine metabolism disorder, namely MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphism. Results: The MTHFR C677T polymorphism had significantly correlation with URPL. Indeed, the frequency of the677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group (p < 0.05). However, the allele, as well as genotype distribution of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms showed no significant difference (p > 0.05). MTHFR 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR 9.0; 95% CI, 2.25-35.99; p = 0.001), while the risk increased 10.0-fold (OR 10.0; 95% CI, 1.8-55.53; p = 0.008) when participants had more than the 3 variant loci. Conclusion: The MTHFR C677T polymorphism was a risk factor for URPL, and determining the MTHFR C677T polymorphism had a potential prediction of URPL risk. Moreover, the MTHFR C677T and MTHFR A1298C joint mutants might have a synergistic effect on URPL. Conversely, there is a lack of evidence suggesting the URPL risk of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms.
... The negative effects of elevated HCY levels on pregnancy are well known, which is associated with a variety of pregnancy complications, such as preeclampsia (PE), early PL (EPL), placental abruption (PA), intrauterine growth restriction (IUGR) and venous thrombosis [32]. Approximately one third of spontaneous abortion before 20 weeks' gestation are associated with elevated HCY levels [33]. ...
Background
For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data.
Methods
A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features.
Results
In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer–Lemeshow test was 7.427, and P = 0.505.
Conclusions
Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability.
Trial registration
This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).
... Because HHcy is a risk factor for vascular diseases examined by our group and other investigators in humans, mouse models, and cell culture (Devlin et al., 2005;Perła-Kaján et al., 2008;Kim et al., 2011;Huang et al., 2012;Gurda et al., 2015), we hypothesize that elevated Hcy may be a potential marker of placental vascular disease. It was reported before that unusually high Hcy levels are linked in humans to pregnancy-related hypertension disorders and unfavorable pregnancy outcomes, including spontaneous abortions (Chamotra et al., 2020), fetal growth restriction, and preeclampsia Gaiday et al., 2018). The mechanism by which HHcy may affect embryo development is insufficient remodeling of the spinal arteries and impaired angiogenesis in the placenta (Burton and Jauniaux, 2018). ...
Hyperhomocysteinemia (HHcy), characterized by elevated homocysteine (Hcy) levels, is a known risk factor for cardiovascular, renal, and neurological diseases, as well as pregnancy complications. Our study aimed to investigate whether HHcy induced by a high-methionine (high-Met) diet exacerbates cognitive and behavioral deficits in offspring and leads to other breeding problems. Dietary HHcy was induced four weeks before mating and continued throughout gestation and post-delivery. A battery of behavioral tests was conducted on offspring between postnatal days (PNDs) 5 and 30 to assess motor function/activity and cognition. The results were correlated with brain morphometric measurements and quantitative analysis of mammalian target of rapamycin (mTOR)/autophagy markers. The high-Met diet significantly increased parental and offspring urinary tHcy levels and influenced offspring behavior in a sex-dependent manner. Female offspring exhibited impaired cognition, potentially related to morphometric changes observed exclusively in HHcy females. Male HHcy pups demonstrated muscle weakness, evidenced by slower surface righting, reduced hind limb suspension (HLS) hanging time, weaker grip strength, and decreased activity in the beaker test. Western blot analyses indicated the downregulation of autophagy and the upregulation of mTOR activity in HHcy cortexes. HHcy also led to breeding impairments, including reduced breeding rate, in-utero fetal death, lower pups’ body weight, and increased mortality, likely attributed to placental dysfunction associated with HHcy. In conclusion, a high-Met diet impairs memory and cognition in female juveniles and weakens muscle strength in male pups. These effects may stem from abnormal placental function affecting early neurogenesis, the dysregulation of autophagy-related pathways in the cortex, or epigenetic mechanisms of gene regulation triggered by HHcy during embryonic development.
... In recent years, some studies found that elevated Hcy was associated with adverse pregnancy outcomes and fetal malformations [11]. HHcy induces hydrogen peroxide and superoxide to produce free radicals, which can cause oxidative damage to vascular endothelial cells, reduce the increase in the number of villous blood vessels, inhibit embryonic blood perfusion, and lead to adverse pregnancy outcomes, such as preeclampsia [12], abortions [13], low birth weight, and increased incidence of type 2 diabetes in the offspring [14]. In addition, Hcy was also proved to be associated with oligohydramnios, fetal growth restriction, and impairment of placental transport [11,15,16]. ...
Objective
To investigate the physiological changes of serum homocysteine (Hcy) levels and to establish trimester-specific reference intervals of serum Hcy levels for Chinese pregnant women.
Method
According to the guideline of the Clinical and Laboratory Standards Institute (CLSI) C28-A3 document, 476 healthy women were recruited in West China Second University Hospital, Sichuan University from January 2021 to October 2021. Among them, 120 were non-pregnant, 118 were in the first trimester, 120 were in the second and 118 were in the third trimester of gestation. The enzymatic cycling method was performed to detect serum Hcy levels. Non-parametric percentiles (2.5th percentile and 97.5th percentile) were calculated to establish the reference intervals for non-pregnant women and pregnant women in different trimester of gestation.
Results
There was a significant statistical difference for serum Hcy levels between non-pregnant women and pregnant women (p < 0.05), and serum Hcy levels in the first, second, and third trimesters of gestation were statistically different (p < 0.05). The trimester-specific reference intervals of serum Hcy levels were 4.35 ∼ 10.16 μmol/L, 3.38 ∼ 8.60 μmol/L, and 3.75 ∼ 11.17 μmol/L for pregnant women in the first, second, and third trimester of gestation, respectively.
Conclusions
Compared to non-pregnant women, serum Hcy levels physiologically decreased after pregnancy, and the physiological changes in serum Hcy levels during pregnancy were also found. Establishing trimester-specific reference intervals of serum Hcy levels for pregnant women was valuable for clinical practice.
... For decades of research on the disease and the ability of clinicians to predict PE, prior to the onset of symptoms, it has not significantly improved [9][10][11]. Guven et al in 2009, demonstrated that Hci levels are higher in patients with pre-eclampsia in the third trimester compared to those of healthy pregnant women [12], therefore it has been suggested that Hci levels could be used as predictors of pre-eclampsia [3,[13][14][15][16][17][18][19]. ...
Homocysteine is an amino acid that is a product of methionine metabolism, is related to preeclampsia in 20-30%, the increase of this or hyperhomocysteinemia may result from the genetic defect of the enzyme methylenetetrahydrofolate reductase involved in the synthesis of homocysteine. Maternal mortality due to preeclampsia is up to 44% and perinatal mortality is reported at up to 27.8%. The objective of this research was to determine homocysteine levels as a predictor of preeclampsia in pregnant women 12 to 20 weeks pregnant. This was an observational, longitudinal and prospective investigation. The study population were patients attending the first antenatal care consultation between 12 to 20ava. weeks, the sample was random that included 360 patients who determined serum homocysteine Sand excluded 48 patients whodid not meet the inclusion and exclusion criteria; they found homogeneity among the patients, 270 patients (86.5%) had a normal evolutionary pregnancy, 27 patients (8.65%) had gestational hypertension, 9 (2.88%) mild preeclampsia and 6 patients (1.9%) severe preeclampsia, none developed HELLP syndrome. Increased homocysteine levels were found in 9 patients who were not related to hypertensive pregnancy disorders. In the present research, homocysteine was not shown to be a predictor of hypertensive disease in pregnancy.
... Окремим видом патології, що впливає на розлади у системі гемостазу, є гіпергомоцистеїнемія [27][28][29]. На відміну від спадкових тромбофілій, при гіпергомоцистеїнемії відсутні початкові зміни у системі гемостазу, розвиток симптомів пов'язаний з прогресуванням вагітності, внаслідок порушення синтезу ферментних систем, накопичення гомоцистеїну у плазмі крові, розвитку оксидантного стресу і порушення перфузії плаценти. ...
The improvement of the providing medical services quality to pregnant women remains an urgent issue in modern obstetrics. Women with perinatal losses deserve special attention, especially in the second half of pregnancy. Changes in the hemostasis system are an integral part of the development of pregnancy. The tendency to hypercoagulation has significant pathogenetic significance and can be the cause of a number of complications – miscarriage in the I trimester of pregnancy and preeclampsia, premature birth, antenatal fetal death (AFD) – in the II and III trimesters of pregnancy. Also, pregnancy is a background process for the activation of a number of diseases, in particular hereditary thrombophilia.The objective: to evaluate the changes in the hemostasis system in women with antenatal fetal death and the effectiveness of the use of low molecular weight heparins for the correction of disorders in the hemostasis system in this category of patients during childbirth and in the postpartum period.Materials and methods. 72 women were examined, including 42 pregnant women with AFD (main group) and 30 pregnant women with a physiological course of pregnancy, childbirth and the postpartum period (control group). The state of the hemostasis system was studied using a standard coagulogram. D-dimer was determined by immunoturbometric analysis.To assess the state of the hemostasis system, the following biochemical tests were used: procoagulant link – fibrinogen content and indicators: prothrombin index, activated partial thrombin time (APTT), thrombin time (TP), ancistrone time (AT), soluble fibrinogen-monomer complex (SFMC), factor X (FX); to evaluate the antithrombin system, the content of antithrombin-III (AT-III), protein C were determined; to characterize the state of the fibrinolytic system – the amount of plasminogen, α2-antiplasmin, fibrinogen degradation products (FDC).Thrombophilia markers and antiphospholipid antibodies were also determined. The preference was given to vaginal childbirth. During childbirth, mechanical compression of the lower limbs was applied using special compression stockings (compression level 2). In 12 hours after delivery thromboprophylaxis with low molecular weight heparins was started, the drug of choice being enoxaparin sodium. After 48 hours of the postpartum period, a comparative analysis of coagulogram indicators was performed to further determine the timing of thromboprophylaxis.Results. Analysis of family thrombotic anamnesis revealed risk factors in 12 (28.6%) patients of the main group. In close relatives of the first line, the presence of peripheral vein thrombosis was found – 5 (41.7%) cases, myocardial infarction under the age of 45 – 3 (25.0%) cases, pulmonary embolism – 1 (8.3%) case, transient ischemic attack of the brain – 3 (25.0%).In the control group only 2 (6.6%) patients had a family history of venous thromboembolism in first-line relatives. The analysis of the coagulation system shows significantly higher fibrinogen values (the main group – 5.3±0.2 g/l, the control group – 4.3±0.1 g/l; p<0.05), functional FX activity (the main group – 149.3±3.1%, control group – 107.3±2.7%; p<0.05), SFMC (main group – 15.9±1.2 μg/ml, control group – 7.8±0.9 μg/ml; p<0.05) and D-dimer (main group – 4.4±0.25 μg/ml, control group – 0.7±0.2 μg/ml; p< 0.05) in pregnant women of the main group. An increase in these indicators is a predictor of thrombus formation, activation of blood coagulation by the internal pathway with a decrease in the antithrombin reserve due to FX.During the correlation analysis, a strong direct relationship (r=0.8633) was established between the indicators of SFMC and FX in the blood serum of pregnant women of the main group, the combination of which determines the tendency to clot formation. Determination of markers for the most common types of thrombophilia shows the dominance of hereditary forms (prothrombin, Leiden mutation, MTHFR) in 43% of pregnant women of the main group.The implementation of the proposed treatment approach contributed to a significant decrease in the average concentration of fibrinogen 48 hours after delivery in postpartum women of the main group (main group: before delivery – 5.3±0.2 g/l, after 48 hours after delivery – 3.9±0.3 g/l; control group: 48 hours after delivery – 3.2±0.2 g/l; p<0.05) in combination with a synergistic decrease in the average indicators of SFMC (main group: before delivery – 15.9±1.2 μg/ml, 48 hours after delivery – 6.2±0.2 μg/ml; control group: 48 hours after delivery – 5.4±0.3 μg/ml; p<0.05) and FX (main group: before delivery – 149.3±3.1%, after 48 hours after delivery – 103.1±3.6%; control group: after 48 hours after delivery – 117.1±4.1%; p<0.05).Conclusions. Increased coagulation function was confirmed in pregnant women with antenatal fetal death (AFD). Thanks to the proposed method of correcting disorders in the hemostasis system, a decrease in the frequency of postpartum thromboembolism in women with AFD is achieved, as well as an improvement in the main indicators of the hemostasis system. This prevents the emergence of a chronic form of the syndrome of disseminated intravascular blood coagulation which is developed in the cases of AFD.
... Polymorphism of the MTHFR gene at position 677C > T has an impact on the function of the MTHRF enzyme in the homocysteine metabolism [101][102][103]. In turn, elevated plasma homocysteine levels have been proven to serve as a risk factor for infertility and pregnancy complications such as miscarriage and preeclampsia [101,[104][105][106]. An association of MTHFR 677C > T and RPL has been reported by researchers [107,108]. ...
Recurrent pregnancy loss is a complex health challenge with no universally accepted definition. Inconsistency in definitions involves not only the number of spontaneous abortions (two or three) that are accepted for recurrent pregnancy loss but the types of pregnancy and gestational age at miscarriage. Due to the heterogeneity of definitions and criteria applied by international guidelines for recurrent pregnancy loss, the true incidence of recurrent miscarriage, which is reported to range from 1% to 5%, is difficult to estimate. Moreover, the exact etiology of recurrent pregnancy loss remains questionable; thus, it is considered a polyetiological and multifactorial condition with many modifiable and non-modifiable factors involved. Even after thoroughly evaluating recurrent pregnancy loss etiology and risk factors, up to 75% of cases remain unexplained. This review aimed to summarize and critically analyze accumulated knowledge on the etiology, risk factors, relevant diagnostic options, and management approach to recurrent pregnancy loss. The relevance of various factors and their proposed roles in recurrent pregnancy loss pathogenesis remains a matter of discussion. The diagnostic approach and the management largely depend on the etiology and risk factors taken into consideration by a healthcare professional as a cause of recurrent miscarriage for a particular woman or couple. Underestimation of social and health consequences of recurrent pregnancy loss leads to compromised reproductive health and psychological well-being of women after miscarriage. Studies on etiology and risk factors for recurrent pregnancy loss, especially idiopathic, should be continued. The existing international guidelines require updates to assist clinical practice.
... Universal screening for GDM is common in most developed nations, using a variety of tests including an oral glucose tolerance test (OGTT) at 24-28 weeks gestation for diagnosis. Serum homocysteine has previously been found to be reduced in all trimesters of pregnancy (due to either a physiological response to the pregnancy, an increase in estrogen, hemodilution from an increased plasma volume, or increased demand for methionine by both the mother and the fetus) compared to non-pregnant controls [7]. Previous studies showed that hyperhomocysteinemia is associated with adverse pregnancy outcomes or early pregnancy losses. ...
Background: In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Therefore, universal screening is widely recommended. Homocysteine levels during pregnancy in women with GDM have been studied; however, it remains unclear whether hyperhomocysteinemia is a useful predictor of GDM. Objective: To determine the association of serum homocysteine level in women with gestational diabetes mellitus. Methods: Case control study was conducted in the Department of Obstetrics and Gynaecology, Institute of Child and Mother Health (ICMH), Dhaka. Pregnant women in their 24 weeks to 40 weeks of gestation attended for antenatal care diagnosed as GDM was selected as cases. Non- diabetic pregnant women matching with cases by age and gestational age were selected as control in this study. GDM was diagnosed by oral glucose tolerance test (OGTT). The serum homocysteine level of these patients was measured. Descriptive and inferential analysis was carried out using SPSS version 22.0. P-value less than 0.05 will be considered as statistically significant. Results: Among the cases fasting blood sugar (6.13 ± 0.66) and controls (4.60 ± 0.57). Similarly, 2 hours after 75 gm. glucose blood sugar among cases (8.46 ± 0.88) and controls (6.32 ± 0.96). Both results were statistically significant p=0.001. Majority of patients were at third trimester of pregnancy (67.0%). 37.5% were primigravida and 2.5% were multigravida. Mean gestational age of cases (30.25 ± 2.74) and controls (30.02 ± 3.03). Among the cases 62.1% had history of GDM where 37.9% don’t have history of GDM. Among control group only 7.7% had history of GDM. This result statistically significant p=0.001. 6.9% cases had history of macrocosmic child which was not statistically significant p=0.49. There was no history of still birth or other congenital defect. Mean serum homocysteine level among cases (6.50 ± 1.72) and controls (5.20 ± 1.87) which was statistically significant p=0.001. Positive correlation observed between maternal serum homocysteine level and maternal blood sugar (r=0.209, p=0.005) in this study. Respondents with high homocysteine level have 3.94 times more chance to develop GDM (OR=3.94; 95% CI = 1.59-9.77). Conclusion: Finding from the present study suggests that maternal elevated serum homocysteine level in pregnancy is significantly associated with Gestational Diabetes Mellitus.
... High levels of homocysteine, an intermediate of methionine metabolism, in humans, was associated with adverse pregnancy and fetal outcomes, including spontaneous abortion and premature delivery [19]. Compared to nonpregnant women, plasma concentration of homocysteine was lower in normal pregnancies [17]. ...
Hydrogen sulfide (H2S) plays a decisive role in kidney health and disease. H2S can ben synthesized via enzymatic and non-enzymatic pathways, as well as gut microbial origins. Kidney disease can originate in early life induced by various maternal insults throughout the process, namely renal programming. Sulfur-containing amino acids and sulfate are essential in normal pregnancy and fetal development. Dysregulated H2S signaling behind renal programming is linked to deficient nitric oxide, oxidative stress, the aberrant renin–angiotensin–aldosterone system, and gut microbiota dysbiosis. In animal models of renal programming, treatment with sulfur-containing amino acids, N-acetylcysteine, H2S donors, and organosulfur compounds during gestation and lactation could improve offspring’s renal outcomes. In this review, we summarize current knowledge regarding sulfide/sulfate implicated in pregnancy and kidney development, current evidence supporting the interactions between H2S signaling and underlying mechanisms of renal programming, and recent advances in the beneficial actions of sulfide-related interventions on the prevention of kidney disease. Modifying H2S signaling is the novel therapeutic and preventive approach to reduce the global burden of kidney disease; however, more work is required to translate this into clinical practice.
... Gaiday et al. had limitations because they did not consider literature written in languages other than English, French, German, and Russian, and they did not subject the collected data to a meta-analysis that might have provided additional information on the levels of homocysteine in pregnancy. The studies were not segmented according to demographic or geographic characteristics [14]. ...
There is already abundant corroboration indicating that elevated serum homocysteine levels may be related to the risk of coronary, cerebral, and peripheral arterial diseases. High homocysteine levels have often been associated with placental vasculopathies and complications related to the placenta, such as fetal growth restriction, Abruption, hypertensive disorders of pregnancy, and recurrent abortions. This scoping review aims to integrate the currently available scientific literature and fill the gaps in our understanding of homocysteine metabolism during pregnancy and its relationship to placenta-mediated complications. Moreover, to summarize the existing literature on the correlation between raised maternal homocysteine levels in early gestation and its association with placenta-mediated complications. We developed this scoping review article by performing a literature review as per the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines and the search was conducted using PRISMA-S (an extension to PRISMA focusing on reporting the search components of systematic reviews) guidelines. The research question was clarified and modified using keywords with important literature published online between 2010 and 2022, which were included from PubMed, and Google Scholar databases with recognized titles and abstracts were examined and cross-checked for case overlap to choose the original reports. A summary of the descriptive data was organized according to the clinical manifestations (symptoms, imaging, and laboratory results) and outcomes (maternal and perinatal). In conclusion, a review of research papers from 2010 to 2022 showed that homocysteine levels during pregnancy fluctuate and are probably influenced by a population's regional, cultural, and socioeconomic status. According to the data, there is an association between elevated homocysteine levels and complications of pregnancies, such as early spontaneous abortions, pre-eclampsia, fetal development restriction, and abruption, as well as in certain cases of maternal and fetal mortality.
... In several patients whose plasma homocysteine levels were compared after surgery, they all had vitamin B12 deficiency. So Plasma homocysteine can be a good parameter for measuring folate-related disorders of the metabolism of cobalamin [10,11]. In a study on 12 patients undergoing surgery, after surgery, the levels of folate and homocysteine increased and methionine was decreased. ...
Nitrous oxide (N 2 O) is an inhaled anesthetic drug that uses during surgery and recently proposed as a treatment for mood disorder in a research setting. Exposure to N2O during surgery can cause hematopoietic and neural side effects. The purpose of this study was to the designation of serum cobalamin, homocysteine and CBC factors changes after exposure to nitrous oxide during orthopedic surgery. This study has been done on 30 patients undergoing orthopedic operations from 2016 until 2018. All patients are scheduled for orthopedic surgery. All patients received nitrous oxide during their anesthesia period. Blood samples were taken from patients 48 hours before surgery and 24 hours after surgery. All samples froze at -20°c immediately after collecting. Then samples transferred to the university laboratory with regards to keeping a cold chain for analysis. Paired T-test and Wilcoxon test were used for comparing vitamin B12, homocysteine, and CBC parameters. Nitrous oxide resulted in marked vitamin B12 and homocysteine level change. Mean concentration of vitamin B12 reduced after exposure to N2O. This difference was significant when analyzed using paired sample T-test (p=0.0001). homocysteine concentration means decreased after exposure to N2O and this difference was statistically significant (p=0.0001). Nitrous oxide will lead to a decrease in vitamin B12 and an increase in homocysteine and mean corpuscular volume in the early postoperative period.
... Trastornos hipertensivos durante el embarazo y puede contribuir al desarrollo de la enfermedad (Gaiday et al., 2018). ...
La obra aborda aspectos importantes como: factores de riesgos, clasificación, algunas condiciones intrínsecas y extrínsecas vinculadas a esta patología, su etiopatogenia y fisiopatología, complicaciones maternas y perinatales; así como sus protocolos de atención, destacándose: el control de la hipertensión arterial, prevención de la convulsión eclámptica, vigilancia biológica y optimización de la extracción; con el propósito de estabilizar a la gestante en espera de la interrupción del embarazo como tratamiento definitivo que será dependiente de la edad gestacional y las condiciones clínicas materno fetales.
... Hyperhomocysteinemia has also been regarded as an important risk factor for thrombophilia [89]. Moreover, multiple common genetic variants in these enzymatic genes have been demonstrated to be associated with increased plasma homocysteine concentrations [90], and the maternal accumulated homocysteine could further damage the endothelium and impair placental function, which may be related to placenta-associated pregnancy complications, such as RPL, placental abruption and preeclampsia [91]. Among these variants, MTHFR C677T and A1298C which contribute to decreased enzyme activities, have been extensively investigated. ...
Recurrent pregnancy loss (RPL) has become an important reproductive health issue worldwide. RPL affects about 2%–3% of reproductive-aged women, and makes serious threats to women’s physical and mental health. However, the etiology of approximately 50% of RPL cases remains unknown (unexplained RPL), which poses a big challenge for clinical management of these patients. RPL has been widely regarded as a complex disease where its etiology has been attributed to numerous factors. Heretofore, various risk factors for RPL have been identified, such as maternal ages, genetic factors, anatomical structural abnormalities, endocrine dysfunction, prethrombotic state, immunological factors, and infection. More importantly, development and applications of next generation sequencing technology have significantly expanded opportunities to discover chromosomal aberrations and single gene variants responsible for RPL, which provides new insight into its pathogenic mechanisms. Furthermore, based upon patients’ diagnostic evaluation and etiologic diagnosis, specific therapeutic recommendations have been established. This review will highlight current understanding and recent advances on RPL, with a special focus on the immunological and genetic etiologies, clinical diagnosis and therapeutic management.
... The majority of Hct, however, is remethylated to yield methionine. This reaction uses 5methyltetrahydrofolate as a donor molecule in most tissues and vitamin B12 as a cofactor for the enzyme methionine synthase [4]. Adenosine triphosphate (ATP) transforms a fraction of methionine to Sadenosylmethionine (SAM). ...
The most extremely unfavourable outcome of pregnancy is the death of the mother and newborn. Negative outcomes for mothers or babies can occur as a result of complications or issues during pregnancy, birth or the post-partum period. Early elevated maternal homocysteine (Hct) levels during pregnancy have been linked to altered placental development. There is evidence that suggests an elevated maternal blood Hct level is the new obstetrical risk factor, and the association between hyperhomocysteinemia (HHct) and numerous obstetrical problems was recently recognised.
Hct is an essential amino acid, which contains sulphur and is formed from the metabolism of methionine. HHct has several known aetiologies, including genetic anomalies; a deficiency in folic acid, vitamin B6 and vitamin B12; hypothyroidism; old age; and renal illnesses. Vascular problems, coronary artery disease, atherosclerosis and embolic illnesses can all occur as a result of high blood levels of Hct. Hct levels are lower in normal pregnancies than it is in women who are not pregnant. Many pregnancy-related problems, including pre-eclampsia (PE), recurrent pregnancy loss (RPL), placental abruption, premature delivery and foetal growth restriction (FGR) have been connected to HHct in recent research.
We looked for pertinent literature using a thorough and systematic search from PubMed, Medline, Embase, Cochrane Library, Google, etc., and articles that were published before August 2022 based on serum Hct levels and various placenta-mediated complications for this review.
In this review, we described the synthesis and metabolism of Hct in humans, Hct levels at various phases of normal pregnancy and the association between Hct and placenta-mediated pregnancy complications.
The outcomes discovered can help obstetricians increase the likelihood of a successful pregnancy in cases where placenta-mediated issues are present. Lowering Hct levels with a high dose of folic acid tablets during the subsequent pregnancy may be useful for women who experienced these difficulties in prior pregnancies as a result of HHct.
... In addition, the fundamental role of Hcy metabolism in the processes of cell division and embryo development has been proven. Freely penetrating the fetoplacental barrier, Hcy can lead to the development of secondary autoimmune reactions, thereby provoking various complications of fetus, including neural tube defects, placental insufficiency, intrauterine growth retardation and low birth weight (Medina et al. 2001;Herrmann and Knapp 2002;Iacobazzi et al. 2014;Mascarenhas et al. 2014;Gaiday et al. 2018). ...
Hyperhomocysteinemia (HHcy) is an autosomal recessive inherited metabolic disease caused by variations in folate metabolism genes, characterized by impaired methionine metabolism and accumulation of homocysteine (Hcy) in the blood serum. It was shown that men usually have higher plasma Hcy levels than women, but have not yet assessed the leading factors of these differences, which is important for the development of personalized protocols for the prevention of folate metabolism disorders in couples with reproductive disorders. This study aimed to analyze the effect of intergenic and gene-factor interactions on the risk of developing HHcy in men and women of married couples with reproductive disorders. In our study were involved 206 married Caucasian couples (206 males and 206 females) from central regions of Ukraine with early pregnancy losses in the anamnesis. We found that the incidence of HHcy in men was significantly higher than in women. Gender differences in folic acid and vitamin B12 levels were identified. The best predictors of HHcy in men (MTRR (A66G), MTHFR (C677T), MTR (A2756G), vitamin B12 level) and in women (MTHFR (C677T), MTR (A2756G), vitamin B12 level) were selected by binary logistic regression. There was no significant difference in the distribution of genotypes by the studied gene variants when comparing men and women with HHcy. Our findings demonstrate that there is a gender difference in the development of HHcy. This difference is caused by intergenic interaction and by environmental factors, in particular, nutrition and vitamins consumption.
... In several patients whose plasma homocysteine levels were compared after surgery, they all had vitamin B12 deficiency. So Plasma homocysteine can be a good parameter for measuring folate-related disorders of the metabolism of cobalamin [10,11]. In a study on 12 patients undergoing surgery, after surgery, the levels of folate and homocysteine increased and methionine was decreased. ...
The promising protective effect of Urtica dioica (U. dioica) extract on different organs' injuries is well established. Nevertheless, its ameliorative activity against cerebral ischemia (stroke) has not yet been clearly evaluated. As such, this study was designed to explore the probable neuroprotective activity of U. dioica on neurological deficit score (NDS), infarct volume (IV) and gene expression of caspase-3 and cyclooxygenases-2 (COX-2) in a rat model of stroke. In this study, twenty-four Wistar rats were randomly arranged into three groups: (1) intact, (2) Middle cerebral artery occlusion (MCAO) control and (3) MCAO + U. dioica (100 mg/kg; daily intraperitoneal (IP) injection for 7 days until one day before induction of MCAO). After 24-h reperfusion, NDS was measured and then the brain tissues were isolated to determine the IV and the mRNA level of COX-2 and caspase-3 genes by 2,3,5-triphenyltetrazolium chloride (TTC)-staining and Real time PCR techniques, respectively. The results showed that pretreatment with U. dioica considerably decreased the NDS and IV in the core, penumbra and subcortex of MCAO-induced rats regarding MCAO rats (P < 0.05). Also, the mRNA level of caspase-3 in the all-mentioned areas of brain was markedly diminished in the U. dioica-treated group in comparison with the MCAO group (P < 0.05). However, COX-2 gene expression was elevated in the subcortex area of MCAO and U. dioica rats in comparison to the intact rats (P < 0.05). Overall, pretreatment with U. dioica might mitigate brain injury after ischemic stroke, most probably by regulating caspase-3 and COX-2 genes expression.
... Any adverse change occurring in a pregnant woman's physical state can complicate her pregnancy and lead to many adverse issues. Various studies have postulated that maternal Hcy-mediated placental thrombosis, inadequate placentation, apoptosis, inflammation, increased oxidative stress, and epigenetic alterations can lead to several pregnancy-linked issues [12][13][14][15][16][17], such as preeclampsia, placental abruption, early pregnancy loss, intrauterine growth restriction, and fetal death [18][19][20]. Normal Hcy values during pregnancy are 3.9 to 7.3 mmol/L before 16 gestational weeks, 3.5 to 5.3 mmol/L during gestational weeks 20 to 24, and 3.3 to 7.5 mmol/L after gestational week 36 [21]. ...
Background
Raised plasma homocysteine (Hcy) levels have been associated with various diseases and pregnancy complications. Preconception is the primary prevention period to prevent birth defects. This retrospective study aimed to investigate the distribution of plasma Hcy levels among men and women at preconception and further evaluate the factors influencing plasma Hcy levels in a Southern China population.
Material/Methods
Sex, age, serum folate levels, plasma Hcy levels, and the time of Hcy and folate detection were obtained by medical records. Univariate analysis and multi-factor mixed virtual linear regression were used to explore the distribution and determinants of plasma Hcy levels.
Results
A total of 3031 participants (1091 men [35.99%] and 1940 women [64.01%]) were included. The average levels of Hcy and the rates of hyperhomocysteinemia (HHcy) in men were higher than those in women (P<0.05). Hcy levels were observed to be lowest during autumn and highest during winter (P<0.05). In the normal Hcy (NHcy) group, serum folate levels were higher than in the HHcy group (P<0.05). Regression analysis suggested that sex, season, and serum folate levels had an effect on Hcy levels, but age was not an influencing factor of Hcy level in the preconception population.
Conclusions
This retrospective study showed that Hcy levels are higher in men and in the winter season. Sex, season, and serum folate levels were the influencing factors of Hcy in the preconception population.
... We observed stronger and more negative associations between % U-iAs, % U-MMAs and C-tAs and birth weight in higher maternal homocysteine strata. Homocysteine is a metabolite of one-carbon metabolism that is independently associated with preeclampsia, intrauterine growth retardation, and other adverse pregnancy outcomes [45,46]. Prior research in adult populations exposed to iAs highlight a relationship between higher levels of homocysteine and lower % DMAs [47,48], reflecting incomplete methylation of iAs to DMAs. ...
Background
Inorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes.
Methods
Data from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011–2012) with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10).
Results
Among urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = − 23.09, 95% CI: − 44.54, − 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = − 28.69, 95% CI: − 53.97, − 3.42) or experiencing hyperhomocysteinemia (β = − 63.29, 95% CI: − 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise.
Conclusions
Tissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs.
... 8,9 Hence, hyperhomocysteine during pregnancy was associated with recurrent pregnancy loss, preeclampsia, and placental abruption. [10][11][12] The human MTHFR gene contains 11 exons located on the short arm of chromosome 1p36.3. The gene encodes for methylenetetrahydrofolate reductase (MTHFR) that catalyzes the irreversible conversion of 5,10methylenetetrahydrofolate to 5-methyltetrahydrofolate. ...
Objective
To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of homocysteine metabolism-related genes in women.
Materials and Methods
A case–control study included 90 women with two or more consecutive unexplained pregnancy losses and 92 controlled women without miscarriage history; the female participants were in the age category of 18–35 years. The high-resolution melting technique was used to detect the single-nucleotide variants related to homocysteine metabolism disorder, namely MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphism.
Results
The MTHFR C677T polymorphism had significantly correlation with URPL. Indeed, the frequency of the677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group (p < 0.05). However, the allele, as well as genotype distribution of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms showed no significant difference (p > 0.05). MTHFR 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR 9.0; 95% CI, 2.25–35.99; p = 0.001), while the risk increased 10.0-fold (OR 10.0; 95% CI, 1.8–55.53; p = 0.008) when participants had more than the 3 variant loci.
Conclusion
The MTHFR C677T polymorphism was a risk factor for URPL, and determining the MTHFR C677T polymorphism had a potential prediction of URPL risk. Moreover, the MTHFR C677T and MTHFR A1298C joint mutants might have a synergistic effect on URPL. Conversely, there is a lack of evidence suggesting the URPL risk of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms.
... However, variations in this gene cause reduction or loss of activity of the MTHFR enzyme leading to global hypomethylation and hyper-homocysteinaemia [21], a sensitive marker of deranged maternal 1-C metabolism, with important consequences also on fertility [93]. Various correlations, in fact, exist between high plasma homocysteine and adverse reproductive outcomes such as RPL [94], pre-eclampsia, placental abruption [95,96], and the prevalence of PCOS [97]. Moreover, a negative correlation is in place between derangements in 1-C metabolism, hyperhomocysteinaemia, and oocyte or embryo development, perhaps via aberrant methylation, but also via oxidative, vascular, apoptotic, and inflammatory pathways [98][99][100]. ...
Increasing evidence on the significance of nutrition in reproduction is emerging from both animal and human studies, suggesting a mutual association between nutrition and female fertility. Different “fertile” dietary patterns have been studied; however, in humans, conflicting results or weak correlations are often reported, probably because of the individual variations in genome, proteome, metabolome, and microbiome and the extent of exposure to different environmental conditions. In this scenario, “precision nutrition”, namely personalized dietary patterns based on deep phenotyping and on metabolomics, microbiome, and nutrigenetics of each case, might be more efficient for infertile patients than applying a generic nutritional approach. In this review, we report on new insights into the nutritional management of infertile patients, discussing the main nutrigenetic, nutrigenomic, and microbiomic aspects that should be investigated to achieve effective personalized nutritional interventions. Specifically, we will focus on the management of low-grade chronic inflammation, which is associated with several infertility-related diseases.
... Apart from inheritable factors, a variety of maternal factors have been found to be related to spontaneous abortion or embryonic chromosomal aberrations, including age, reproductive history, and immune or endocrine dysfunction [1][2][3]9]. In addition, elevated maternal serum level of homocysteine was shown to increase the risk of fetal loss and stillbirth [10]. Supplementation of folic acid can decrease the concentration of homocysteine and reduce the risk of pregnancy loss [11,12]. ...
Background
Most embryos that spontaneously abort during early pregnancy are found to have chromosomal abnormalities. The purpose of this study is to explore the factors involved in chromosome aberrations during embryogenesis.
Methods
A case-case study was performed to compare the risk factors for spontaneous abortion with and without embryo chromosome aberration. A total of 160 cases of spontaneous abortion were enrolled from a tertiary general hospital in Kunming. KaryoLite BACs-on-Beads (KL-BoBs) and fluorescence in situ hybridization (FISH) were employed to determine chromosomal constitution of abortion chorion villus samples. Maternal serum levels of homocysteine (Hcy) were detected by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Information about clinical background and environmental exposure was collected through a self-designed questionnaire. To identify the inherited chromosomal abnormalities, couples with chromosomal abnormalities in abortus were recalled for karyotyping.
Results
The overall rate of chromosomal abnormalities was 62.5% (100/160, KL-BoBs combined with FISH) including 51.9% (83/160) aneuploidies, 6.3% (10/160) polyploidies, and 4.4% (7/160) structural abnormalities. Only one case of structural abnormality was found to be inherited from maternal balanced translocation. Compared to abortus with normal karyotype, abortus with abnormal karyotype showed a positive association with parental age and elevated maternal serum homocysteine (Hcy) level, but negative association with previous miscarriage and perceived noise.
Conclusions
Embryonic chromosomal aberrations accounted for the majority of spontaneous abortion cases. A combination of internal and external factors may induce spontaneous abortion through fetal chromosomal aberrations or other pathogenic mechanisms.
... Under certain temperature and pressure, the determination of the amount of carbon dioxide in dissolving to the plasma or serum is CO 2 , which is mainly used to estimate the content of sodium bicarbonate in blood, to assess the imbalance of acid-base balance and its degree, and to determine the function of regulating the balance of acid and alkali in the kidney [14]. Hcy is an amino acid containing sulfur, which is demethylated by methionine and is an intermediate product of methionine metabolism and excretes from the kidneys [15]. The characteristics of blood, metabolic system and circulating metabolism of Hcy in pregnancy make plasma Hcy level closely related to the occurrence and development of pregnancy-related diseases [16]. ...
Objective
This cross-sectional study aims to explore variation trend of renal function for healthy pregnant women at different gestational age, and to establish RIs of renal function set tests according to trimester of pregnancy.
Methods
A total of 120 healthy pregnant women and 40 healthy non-pregnant women were enrolled, divided into early trimester (1-13 weeks of gestation, n=40), second trimester (14-27 weeks of gestation, n=40), third trimester (≥28 weeks of gestation, n=40), and non-pregnant women group (n=40). Analytes of UA, BUN, Cr, β2-MG, Cys-C, RBP, NAG, CO2, HCY, CG, C1q and NGAL were measured using the analytical systems in Second Xiangya Hospital. The RIs were defined using non-parametric 95% intervals.
Results
The RIs for UA, Cr, β2-MG, NAG, CO2, Hcy and C1q were established respectively for the first and second trimester group and the third trimester group, there are huge differences after pregnancy. The RIs for BUN was different for 1-13 weeks and after 14 weeks. There are significant differences for NGAL for pregnant and non-pregnant women but not for Cys-C and RBP.
Conclusion
The RIs for renal function tests in pregnant women were established, thus providing clinical reference intervals for the clinicians.
... We all agree that it should be used judiciously; on the other hand our experience does support the use of LMWH and low dose aspirin (LDA) in selected cases of recurrent pregnancy loss. Hyperhomocysteinemia has also emerged as a strong risk factor for RPL and it has a correlation with complications such as spontaneous abortion fetal death, preeclampsia and placental abruption etc. 1 dose aspirin has shown improvement in live birth rate and decline in associated morbidities like preeclampsia eclampsia, intrauterine growth restriction (IUGR) and prematurity in patients with APLA syndrome. 2 Vitamin B12 3000mg and folic acid supplementation in patients with hyperhomocysteinemia along with thromboprophylaxis also gives good obstetric outcome. ...
Objective: The purpose of the study was to see the effect of low molecular weight heparin (LMWH) and low dose aspirin (LDA) in recurrent pregnancy losses (RPL) due to antiphospholipid antibody (APLA) / Pre APLA syndrome and hyperhomocysteinemia. Method: A total number of 138 women presenting in pregnancy with previous two or more consecutive pregnancy losses with APLA / Pre APLA syndrome or with hyperhomocysteinemia (HHCY) were included in the study. APLA tests and serum homocysteine levels were done in all cases. Patients were put on LMWH 40mg sc/day and tab aspirin 150mg/day after the cardiac activity was noted and continued till twelve hours before planned delivery. In cases of hyperhomocysteinemia vitamin B12 and folic acid supplementation was given along with thromboprophylaxis. Results: Out of 138 women with RPL, 105 (76.07%) had recurrent abortions while 52 (37.68%) had history of intrauterine deaths in past pregnancy along with obstetric complications like preeclampsia, IUGR etc. APLA test was positive in 42 women (30.43%) while it was negative in 86 (67.18%) women. Hyperhomocysteinemia was present in 10 (7.24%) women. Women who received thromboprophylaxis the outcome in index pregnancy was, 94.20% i.e. 130 women had successful pregnancy outcome (live births) while 8 women (6%) had pregnancy loss in spite of thromboprophylaxis and vitamin B12 supplementation. Conclusion: Combination treatment with LDA and LMWH in women with APLA / Pre APLA syndrome and additional vitamin B12 and folic acid supplementation in hyperhomocysteinemia significantly improves the pregnancy outcome in patients with recurrent pregnancy loss with success rate of 94%.
Цель исследования: оценка возможности прогнозирования тяжести преэклампсии (ПЭ) на основании концентраций плацентарного фактора роста (placental growth factor- PLGF) в моче в сравнении с концентрациями PLGF в крови, определенных в первом триместре беременности. Материалы и методы: проведено одноцентровое проспективное когортное исследование, в которое были включены 288 беременные без факторов риска развития ПЭ. Всем исследуемым проведено общеклиническое обследование и оценка предыдущих событий со здоровьем. Диагностика ПЭ и оценка ее тяжести проведена согласно критериям Международного общества по изучению гипертонии у беременных. Уровни PLGF в крови и моче определены в сроке гестации 10-14 недель, иммуноферментным анализом на анализаторе Dialab ELX808IU (Dialab, Австрия) с использованием реактивов Human Placental Growth Factor ELISA Kit (Sigma Aldrich, Германия). Результаты: были выявлены в 2,8% (n = 8) умеренная ПЭ и 2,4% (n = 7) тяжелая ПЭ, а 94,8% (n = 273) пациентов на протяжении всей беременности были нормотензивными. Концентрация мочевого PLGF составили при умеренной ПЭ 7,97 (6,35-27,21) пг/мл и не были статистически различимы с нормотензивными беременными, где уровень мочевого PLGF составил 21,4 (14,3-35,1) пг/мл, а также с уровнем сывороточного PLGFпри умеренной ПЭ (p > 0,05). При тяжелой ПЭ концентрации мочевого PLGF составили 7,17 (5,24-16,2) пг/мл и были статистически ниже, в сравнении с нормотензивными беременными (p < 0,05) и с сывороточным PLGF (p = 0,0233). ROC-анализ показал оптимальные уровни отсечки при тяжелой ПЭ для мочевого PLGF ≤ 10,8 пг/мл, с диагностическими показателями AUC 0,869, p < 0,0001, Se 71,4%, Sp 87,2%, DOR 16,8. Выводы: определение мочевого PLGF в первом триместре беременности может быть использовано для прогнозирования тяжелой ПЭ, но не для умеренной ПЭ, а также может быть использовано для разработки экспресс тест-систем. Ограничения настоящего исследования требуют дальнейшего изучения мочевого PLGF для прогнозирования ПЭ и ее тяжести.
Objective: assessment of prediction of the severity of preeclampsia (PE) based on the concentration of placental growth factor (PLGF) in urine in comparison with the concentrations of PLGF in the blood, determined in the first trimester of pregnancy. Materials and methods: it was a single-center prospective cohort study, included 288 pregnant women without risk factors of PE, selected by a simple random sample. All subjects underwent general clinical examination and assessment of previous health events. Diagnosis of PE and assessment of its severity were carried out according to the criteria of the International Society for the Study of Hypertension in Pregnancy. PLGF levels in blood and urine were determined at a gestational age of 10-14 weeks by ELISA by the Dialab ELX808IU analyzer (Dialab, Austria) using Human Placental Growth Factor ELISA Kit reagents (Sigma Aldrich, Germany). Results: There were 2.4% (n = 7) mild PE, 2.8% (n = 8) severe PE, and 94.8% (n = 273) of patients were normotensive during pregnancy. The concentrations of urinary PLGF were 7.97 (6.35-27.21) pg/ml in mild PE and was not statistically different from normotensive patients, where the level of urinary PLGF was 21.4 (14.3-35.1) pg/ml, as well as with the level of serum PLGF with mild PE (p> 0.05). In severe PE, urinary PLGF concentrations were 7.17 (5.24-16.2) pg/ml and were statistically lower in comparison with normotensive pregnant women (p < 0.05) and with serum PLGF (p = 0.0233). ROC-analysis showed optimal cut-off levels in severe PE for urinary PLGF ≤ 10.8 pg/ml, with diagnostic indicators AUC 0.869, p <0.0001, Se 71.4%, Sp 87.2%, DOR 16.8. Conclusions: determination of urinary PLGF in the first trimester of pregnancy may be used to prediction of severe PE, but not for mild PE, and may be used to develop express test systems. The limitations of this study warrant further study of urinary PLGF to predict PE and its severity.
Зерттеу мақсаты: преэклампсия ауырлығын болжау мүмкіндігін бағалау жүктіліктің бірінші триместрнде анықталған зәрдегі плацентарлық өсу факторының концентрациясы негізінде қандағы PLGF концентрациясымен салыстыру арқылы. Материалдар мен әдістер: бір орталықтандырылған проспективті когортты зерттеу жүргзілді,оған Прэклампсия даму қаупі жоқ 288 жүкті әйел қосылды. Барлық зерттелушілерге жалпы клиникалық тексеру жүргізілді және денсаулыққа қатысты өткен жағдайлар бағаланды. Преэклампсия диагностикасы және оның ауырлығын бағалау жүктілерде гипертонияны бағалаудың халықаралық қоғам ұсынған критерияларға сәйкес жүргізілді. Қандағы және зәрдегі PLGF деңгейі жүктіліктің 10-14 аптасында анықталды, иммуноферментті талдау DialabELX808IU (Dialab, Австрия) анализаторында, Human Placental Growth Factor ELISA Kit (Sigma Aldrich, Германия) реактивін қолдану арқылы жүзеге асырылды. Нәтижесі: анықталды 2,8% (n = 8) жеңіл ПЭ және 2,4% (n = 7) ауыр ПЭ, ал 94,8% (n = 273) науқаста жүктілік бойына нормотензивті. Зәрдегі PLGF концентрациясы жеңіл ПЭ 7,97 (6,35 - 27,21) пг/мл құрайды және нормотензивті жүктілермен статистикалық айырмашылықтар болмады, зәрдегі PLGFдеңгейі 21,4 (14,3-35,1) пг/мл құрайды, сондай-ақ сарысулық PLGF деңгейі жеңіл ПЭ кезінде (p>0,05). Ауыр ПЭ кезінде зәрдегі PLGF 7,17 (5,24 - 16,2) пг/мл құрайды және статистикалық төмен болды,нормотензивті жүктілермен салыстырғанда (p< 0,05) және сарысулық PLGF (p = 0,0233) ROC-талдауы ауыр ПЭ кезінде қолайлы шектеу деңгейін көрсетті зәрдегі PLGF ≤ 10,8 пг/мл, диагностикалық көрсеткіштерімен AUC 0,869, p < 0,0001, Se 71,4%, Sp 87,2%, DOR 16,8. Қорытынды: жүктіліктің бірінші триместріндегі зәрдегі PLGF анықтау ауыр ПЭ болжамында қолданылуы мүмкін,тек жеңіл ПЭ үшін емес, сондай-ақ эксперсс тест-жүйесін жасауда қолданылуы мүмкін. Қазіргі зерттеудің шектелуі зәрдегі PLGF зерттеу ПЭ болжамы және оның ауырлығын анықтау үшін оның әрмен қарай зерттелуін қажет етеді.
Background:
The aim of this study was to investigate the methylenetetrahydrofolate reductase (MTHFR) 677 C > T gene polymorphism in term infants born small (SGA), appropriate (AGA), and large for gestational age (LGA).
Methods:
The study comprised 165 newborns with SGA, LGA and AGA. Genomic DNA was isolated from the peripheral blood. Samples were genotyped for MTHFR 677 C > T gene polymorphisms using PCR-RFLP.
Results:
There was a statistically significant difference between the genotype and their allelic distribution of AGA, SGA, and LGA. The newborns carrying the TT genotype had higher birth weight than those carrying the CC and CT genotypes. The frequency of MTHFR 677 TT genotype and T allele was significantly higher and was found to be linked with a higher risk in LGA than in the AGA group.
Conclusions:
The MTHFR 677 C > T gene polymorphism can be used as a genetic marker in Turkish LGA newborns, but not in SGA.
Recent research has made it possible to expand and complement the modern understanding of the regulation of many physiological processes of the body. At the same time, there are many controversial questions about the role of increasing homocysteine levels in the development of certain diseases, mainly cardiovascular pathology. Purpose. To analyze the current literature on the contribution of hyperhomocysteinemia to the formation of cardiovascular diseases (CVD). Material and methods. The data of foreign and domestic articles on the research topic found in Pubmed and eLibrary and published over the past 7 years are analyzed. Conclusions. Hyperhomocysteinemia leads to amplification of the adverse effects of classical CVD risk factors such as hypertension, smoking, lipid metabolism by participating in the formation of endothelial dysfunction.
Aims
The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear.
Materials and Methods
In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase ( MTHFR ) gene were genotyped.
Results
Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large‐for‐gestational age (LGA), preterm birth (PTB), and reduced gestational age ( p < 0.05). Pregnant women with MTHFR A1298C AA or C677T CT + TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32‐times and reduced the gestational age by 0.11 weeks ( p < 0.05). For MTHFR C677T CC + TT genotype carriers, higher HbA1c levels were associated with 1.49‐, 1.24‐, and 1.23‐times increased risks of macrosomia, LGA, and PTB, respectively ( p < 0.05). A U‐shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC + TT participants, with a cut‐off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT + TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37‐times increased risks of LGA and PTB, respectively.
Conclusions
Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large‐scale studies are required to confirm these findings.
Introducción: El objetivo del presente estudio fue evaluar la homocisteína como predictor de pre eclampsia en embarazos de 12 a 20 semanas de gestación. Métodos: Se trató de una investigación observacional, longitudinal y prospectiva. La población en estudio fueron pacientes que asistían a la primera consulta de control prenatal entre las 12 a 20ava. semanas, la muestra fue aleatoria que incluyó 360 pacientes que se determinó la homocisteína sérica. Se excluyeron 48 embarazadas que no cumplieron con los criterios de exclusión e inclusión. Resultados: Se encontró homogeneidad entre las pacientes, 270 pacientes (86.5%) tuvieron un embarazo normal, 27 mujeres (8.65%) tuvieron hipertensión gestacional, 9 (2.88%) pre eclampsia leve y 6 pacientes (1.9%) pre eclampsia severa, no se observó casos de síndrome de HELLP. Se observó incremento de los niveles de homocisteína en 9 mujeres que no tuvieron relación con trastornos hipertensivos de la gestación. Conclusiones: En la investigación presente no se expresó que la homocisteína sea un predictor de enfermedad hipertensiva del embarazo.
: This study was carried out to determine the association of folic acid deficiency, vitamin B12 deficiency, hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with obstetrical events linked to folic acid deficiency like neural tube defects (NTD); unexplained abruption placentae (AP), recurrent pregnancy loss (RPL) and preterm labour(PTL).
: In the present study 87 pregnant females with past or present history of either neural tube defect (NTD), abruptio placentae, recurrent pregnancy loss (RPL) or preterm labour and 100 pregnant females without any such history were enrolled. Serum levels of folic acid, vitamin B12 and homocysteine in these females were estimated using chemiluminescence and Polyacrylamide gel electrophoresis (PAGE) was used to detect MTHFR gene polymorphism.
: No significant association was observed between serum folic acid levels and NTD (p = 0.495), RPL (p = 0.832) or preterm labour (p = 0.724). However, folic acid deficiency had significant association with the occurrence of abruptio placenta (p = 0.001). Serum vit B12 deficiency was found to be a significant risk factor only in patients with RPL. Increased homocysteine revealed significant association with RPL (p= 0.024), abruption placentae (p=0.002) and preterm labour (0.015). No polymorphism in MTHFR gene could be revealed in the above pregnancy complications.
: In the present study, deficiency of folic acid was uncommon probably due to its routine supplementation throughout the first trimester. However, preconceptional folic acid supplementation still needs to be emphasized to build up adequate folic acid levels required during embryogenesis. The relationship between vit B12 and RPL needs studies on larger number to establish the association before supplementation is suggested. MTHFR677 gene polymorphism may have remained undetected due to small sample size.
The hemostasis system is composed of procoagulant, anticoagulant, and fibrinolytic proteins that interact with endothelial and blood cells and with each other in a complex system of checks and balances to maintain blood flow while preventing both hemorrhage and thrombosis. Pregnancy is a unique physiological state in which biological alterations predispose both mother and fetus to both bleeding and clotting. The placenta is a vascular interface for maternal and fetal blood exchange which predisposes the mother to hemorrhage. Maternal hemostasis presents a compensatory hypercoagulability including elevated factor VIII, von Willebrand factor, fibrinogen and thrombin generation, decreased thrombin regulation with resistance to activated protein C and decreased free protein S, and decreased fibrinolysis with increased plasminogen activator inhibitors. The placental vascular surface is of fetal trophoblastic origin that derives many characteristics of endothelium but differs in that tissue factor is constitutively expressed. Ontogeny of fetal hemostasis is characteristic. Platelets, von Willebrand factor, factor VIII, and fibrinogen are expressed and mature early in gestation, while vitamin K–dependent and contact factors exhibit delayed development. The fetal hemostatic system has a decreased capacity to generate or regulate thrombin, resulting in a fragile balance with little capacity to compensate under stress conditions, particularly in the infant born prematurely. Dysfunction of the maternal/placental/fetal unit gives rise to gestational disorders including preeclampsia, fetal growth restriction, placental abruption, and premature delivery. Knowledge of normal hemostasis levels and function are critical to evaluate bleeding or clotting syndromes in the pregnant woman and her fetus or newborn infant.
Objective:
Uterine arterial blood flow is an important factor in embryonic development. Increased uterine artery blood flow resistance may be related to vascular damage. Homocysteine (HCY) can induce injury of endothelial through various pathways. Therefore, we investigate the association between serum HCY levels and uterine artery blood flow in the non-pregnant state in women who have experienced pregnancy loss (PL).
Methods:
364 women eligible for PL were included in the study. The detection of HCY was completed by the Laboratory of Lanzhou University Second Hospital. We divided the patients into three groups: Low-HCY (HCY<10 umol/L, n=144), Medium-HCY (HCY 10∼15 umol/L, n=174) and High-HCY (HCY>15 umol/L, n=46). The patients were subjected to vaginal color Doppler ultrasonography to measure bilateral uterine artery resistance index (RI), pulsatility index (PI) and peak systolic velocity/end diastolic velocity (S/D).
Result:
Among 364 women, the right uterine artery RI in L-HCY, M-HCY, and H-HCY groups were 0.78±0.08, 0.79±0.07 and 0.81±0.07, respectively (P=0.04). The left uterine artery RI in L-HCY, M-HCY, and H-HCY groups were 0.78±0.08, 0.81±0.07 and 0.81±0.07, respectively (P=0.01). The right uterine artery RI level and the left uterine artery RI was significantly associated with HCY level (r = 0.103, P =0.050; r = 0.104, P =0.047, respectively). Of these, 177 women experienced their next pregnancy, and 33 patients experienced PL again. The pregnancy rate in L-HCY, M-HCY, and H-HCY groups were 47.92% (69/144), 49.43% (86/174) and 47.83% (22/46), respectively (P=0.95). In next pregnancy, the PL rate in L-HCY, M-HCY, and H-HCY groups were 8.70% (6/69), 22.58% (22/86) and 22.73% (5/22), respectively (P=0.03).
Conclusion:
HCY can increase the uterine artery resistance in the non-pregnant state and is associated with the abortion rate of next pregnancy.
Background: Premature rupture of membranes (PROM) has been a problem in obstetrics since ancient times until now. The incidence of PROM in the world ranges from 5% - 15% of all pregnancies, while the incidence in developing countries, especially Indonesia ranges from 4.5% to 7.6% of all pregnancies. Preterm is one of the highest contributors to perinatal mortality and morbidity. The incidence of preterm pregnancy in the world is around 9.6% of all births, while in Southeast Asia is around 11.1% It has been shown to have a significant effect on vascular endothelial pathology. Methods: The study was conducted with an analytic cross-sectional design involving 70 respondents of pregnant women with gestational age of 20 - < 37 weeks with and without PPROM who came to the outpatient clinic and maternity ward of Prof. Dr. I.G.N.G. Ngoerah Hospital Denpasar from May 2021 – July 2021. Results: The results of the analysis of this study found a statistically significant relationship between homocysteine (Hcy) levels and the incidence of preterm premature rupture of membranes (p = 0.001). The prevalence ratio value of 2.2 means that high homocysteine levels is a risk factor for premature rupture of membranes in preterm pregnancy (RP = 2.2; 95% CI = 1.33-2.94; p = 0.001). Conclusion: High homocysteine level is a risk factor for premature rupture of membranes in preterm pregnancy. Latar Belakang: Ketuban pecah dini (KPD) preterm merupakan masalah di bidang obstetrik sejak dahulu sampai sekarang. Insiden KPD di dunia berkisar antara 5% - 15% dari seluruh kehamilan. Insiden KPD di negara berkembang khususnya Indonesia berkisar 4,5% - 7,6% dari seluruh kehamilan. Kehamilan preterm menjadi salah satu penyumbang tertinggi angka mortalitas dan morbiditas perinatal. Insiden kehamilan preterm di dunia sekitar 9.6% dari semua kelahiran, sedangkan di Asia tenggara terdapat sekitar 11,1%. Hcy telah terbukti signifikan berpengaruh pada patologi endotel pembuluh darah. Metode: Penelitian dilakukan dengan rancangan cross sectional analitik dengan melibatkan 70 responden wanita hamil dengan usia gestasi 20 - <70 minggu dengan atau tanpa KPD yang dating ke poliklinik dan ruang bersalin RSUP Prof. Dr. I.G.N.G. Ngoerah bulan Mei 2021 – Juli 2021. Hasil: Diperoleh hubungan bermaksana secara statistik antara kadar homocycteine dengan kejadian ketuban pecah dini pada kehamilan preterm (p = 0, 001), dan rasio prevalensi 2,2 berarti kadar homosisteine yang tinggi merupakan faktor risiko terjadinya ketuban pecah dini pada kehamilan preterm (RP = 2.2; 95% CI = 1.33-2.94; p = 0.001). Kesimpulan: Kadar homosistein yang tinggi merupakan faktor risiko terjadinya ketuban pecah dini pada kehamilan preterm.
Background:
Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls.
Methods:
In 53 women of RPL group and 50 controls, the genetic analysis was performed. The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed.
Results:
The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively).
Conclusion:
There is a significant association between the risk of RPL and miR-449b/TNF-α combination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.
Objective:
We aimed to investigate the correlation between blood homocysteine (Hcy) levels and pre-eclampsia (PE) risk in pregnant women.
Methods:
Related articles were searched using PubMed, Embase, and Web of Science databases. Methodological quality of included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). Cochran's Q and I2 tests were used to evaluate heterogeneity. Egger's test was used to evaluate publication bias. A sensitivity analysis was performed to test stability of the results using a one-by-one elimination method. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess certainty of evidence.
Results:
Nine studies (4384 PE and 26021 non-PE patients) were included in the meta-analysis. The methodology of them was of good quality, with NOS scores of 5-8. However, there was a significant heterogeneity among included studies. Therefore, the random effect model was generated and combined results suggested a significant association between increased level of Hcy in pregnant women and PE risk. Although a significant publication bias was found in the current study with a P value of 0.006 in the Egger test, sensitivity analysis showed that the combined results were stable and did not vary significantly from any single study. However, the GRADE evidence quality was very low, which may lower the recommendation of pooled results.
Conclusions:
Increased levels of Hcy in maternal blood were significantly associated with the risk of PE, but low certainty of evidence need to be improved by more high-quality studies.
Evidence suggests a potential relationship between gestational weight gain (GWG) and adverse birth outcomes. However, the role of maternal genetic polymorphisms remains unclear. This study was conducted to investigate whether the relationship of GWG with risk of adverse birth outcomes was modified by methylenetetrahydrofolate reductase (MTHFR) polymorphisms. A total of 2,967 Chinese pregnant women were included and divided into insufficient, sufficient, and excessive groups based on the Institute of Medicine (IOM) criteria. Polymorphisms of C677T and A1298C in gene MTHFR were genotyped. Multivariable logistic regression models were introduced after controlling major confounders. Excessive GWG was found to increase the odds ratio (OR) for macrosomia [OR = 3.47, 95% confidence interval (CI): 1.86–6.48] and large-for-gestational age (LGA, OR = 3.25, 95% CI: 2.23–4.74), and decreased the OR for small-for-gestational age (SGA, OR = 0.60, 95% CI: 0.45–0.79). Pregnant women with insufficient GWG had a higher frequency of SGA (OR = 1.68, 95% CI: 1.32–2.13) and a lower rate of LGA (OR = 0.51, 95% CI: 0.27–0.96). Interestingly, significant associations of GWG categories in relation to low birth weight (LBW), macrosomia, and SGA were only suggested among pregnant women with MTHFR A1298C AA genotype. Among pregnant women with insufficient GWG group, an increased risk of 3.96 (95% CI: 1.57–10.01) for LBW was observed among subjects with the A1298C AA genotype, compared to the AC+CC genotype group. GWG categories are closely related to LBW, macrosomia, SGA and LGA, and the associations were modified by the polymorphism of MTHFR A1298C.
Environmental toxins are all around us. Research with cord blood has shown that most newborns are born with hundreds of chemicals in their circulation, demonstrating significant exposure.1 Most research to date has focused on the effects on the fetus, but we are also beginning to understand the negative impact that these substances have on pregnancy and maternal health.
Exposure to environmental toxins during pregnancy such as heavy metals and endocrine disruptors is associated with increased rates of pre-eclampsia (PE).2 PE is diagnosed in 2-10% of pregnancies worldwide and is a leading cause of preterm birth, stillbirth, and maternal mortality around the world.3
The etiology of PE is not yet known and is generally considered to be multi-factorial.4 PE appears to involve abnormal placentation,5 abnormal liver function,3,6 inflammation, especially of the endothelium,4 and cardiovascular risk factors such as high homocysteine levels.4,7 A combination of reducing exposure to the toxins and supporting the body’s ability to eliminate them may be a way to reduce pre-eclampsia risk.
Objectives:
This presentation exists to highlight known links between environmental factors and pre-eclampsia, share published findings that can help nutritionally support pregnant women in reducing their risk of pre-eclampsia, and to propose additional nutritional interventions to be investigated.
Objective: In our study, we aimed to evaluate the knowledge, attitudes and behaviors of pregnant women about tetanus vaccine
who admitted to our hospital.
Methods: The pregnant women who admitted to our clinic between
January 2019 and July 2019 were included in this cross-sectional
study. All participants took a questionnaire evaluating tetanus vaccine rates during pregnancy and the knowledge, attitude and behaviors of pregnant women about tetanus vaccine.
Results: A total of 227 pregnant women were included in the study.
The mean age of the patients was 29.5±6.12, and the mean week of
gestation was 30.79±7.49. It was found that 24 (52.1%) of the 46
(12.6%) patients who were not vaccinated for tetanus in their previous
pregnancies believed that the vaccine was harmful for the baby and
therefore they were not vaccinated. In addition, it was found that the
physicians who carried out the follow-ups of 2 of these 46 patients,
who stated that they were not vaccinated in their previous pregnancies, were also anti-vaxxers. It was found out that 172 (75.7%) patients
learnt from the family practitioner’s nurse that they needed to be vaccinated. The number of the patients who learnt from the obstetriciangynecologist that they needed to get tetanus vaccine was only 2
(0.8%). While there were 177 (77.9%) patients who were / will be vaccinated for tetanus in this pregnancy, 47 (20.7%) patients were indecisive for being vaccinated or not. Also, 200 (88.1%) patients knew
that tetanus vaccine does not have any side effect on pregnancy.
Conclusion: The greatest obstacles to the vaccination are the belief
that vaccine may harm the baby, and the lack of knowledge about vaccination. The greatest obstacle caused by the healthcare professionals
is the lack of providing sufficient information about vaccine, not
explaining the necessities of vaccine to patients and the perception of
obstetricians in particular that only the primary healthcare organizations are responsible for tetanus vaccine
Objective To assess homocysteine (Hcy) levels in the three trimesters of pregnancy in women with fetal growth restriction (FGR) and to evaluate the role of Hcy as a possible predictor of FGR.
Methods A total of 315 singleton pregnant women were included in the present prospective cohort study and were monitored since the 1st trimester of pregnancy before delivery. Newborns were monitored for the first 7 days of life. Patients who had risk factors for FGR were excluded. Fetal growth restriction was defined according to uterine fundal height (< 10 percentile), ultrasound fetometry (< 5 percentile), and anthropometry of newborns (< 5 percentile). The concentrations of Hcy were detected at between 10 and 14, between 20 and 24, and between 30 and 34 weeks of pregnancy by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristics (ROC) curve test and diagnostic odds ratio (DOR) were performed to evaluate the results of ELISA.
Results The concentration of Hcy in patients with FGR was 19.65 umol/L at between 10 and 14 weeks, compared with 9.28 umol/L in patients with normal fetal growth (p < 0.0001). The optimal cut-off level for Hcy in the 1st trimester of pregnancy was > 13.9 umol/L with AUC 0.788, sensitivity of 75%, specificity of 83.6%, and DOR of 15.2.
Conclusion Assessment of serum Hcy concentration may be used as a predictor of FGR, with the highest diagnostic utility in the 1st trimester of pregnancy.
Introduction. Dolichoarteriopathy of the internal carotid artery (DICA) is not a rare disease, despite the half-century history of studying this nosology, some questions regarding the etiology, clinic, diagnosis and treatment tactics remain unanswered. Aim. A review of the literature on the optimization of the etiology, clinical picture, diagnosis, and treatment tactics of DICA.
Search strategy. In the course of studying this pathology, a search was carried out for the current literature of the PubMed database (MEDLINE) and the scientific electronic library "CyberLeninka" (CYBERLENINKA) and eLIBRARY.RU with a search depth of 20 years (2001–2021). In some cases, there are links to earlier publications of historical value. The literature search included publications in Russian and English. A total of 488 sources were found, of which 52 were selected that meet the inclusion criteria and exclude newspaper publications, case reports, abstracts, and duplication or repetition of information.
Results. The article presents the main hypotheses for the development of congenital and acquired DICA. The diversity of the clinical picture of this pathology is shown. Various instrumental methods for the diagnosis of DICA are presented, with the advantages and disadvantages of each of them. The tactics of treatment of DICA with modern methods of reconstruction of the carotid artery (CA) are considered.
Conclusions. To date, there is no unequivocal opinion about the etiology. Narrowing of the lumen at the site of the bend of the artery reduces blood flow through the ICA and can cause the development of general cerebral symptoms. Diagnostics of DICA include ultrasound and radiation methods, but there is no standardized algorithm for examination methods. Symptomatic DICA with instrumental proven hemodynamically significant deformity should be treated surgically. Surgical treatment of DICA can lead to good results, with low morbidity and mortality.
t was shown that the pleonasm of myoma myocytes is one of the main processes that cause an increase
in the mass of the tumor. In spite of the fact that momentous cells show similarity with cells of the
myometrium, differences in the structure and metabolism of these tissues were unearthed. The paper
presents an analysis of the morphological structure of uterine leiomyoma with a view to establishing its
pathogenesis. 93 in-treatment patients diagnosed with uterine myoma took part in the research. 60
extirpated uteruses were morphologically investigated. The statistical processing of data included
estimation of the arithmetic mean (M), the average error of mean (m) as well as the frequency of the
occurrence of features with discrete values. Student’s t-test was used as well as Pearson’s chi-squared
test and Fisher’s exact test, the method of multiple intergroup differences, multiple regression analysis
and linear discriminant analysis. The modern studies substantially expand our idea of the risk factors
and the mechanisms of development of uterine leiomyoma. A comprehensive approach to the study of the
myoma provides new data on the prevalence and causes of this disease. One of the main outcomes of the
analysis of contemporary data on uterine leiomyoma is the fairly clear interdependence between the
character of the growth and the enlargement the tumor as well as the development of multifaceted
changes on the systemic and local levels.
Keywords: Myoma, Uterus, Reproduction, Histology, Histochemistry, Etiology, Degeneration, Cell
Necrobiosis, Denervation.
In this study, the association of high homocysteine concentrations (>10 μmol/L) of pregnant women with hypertensive disorders during pregnancy was studied, as well as other complications of pregnancy, such as loss of pregnancy in the first half, premature birth, intrauterine growth retardation, congenital malformations development of the fetus. A single-center prospective cohort study was conducted. Depending on the concentration of homocysteine detected by the immunoenzyme assay with monoclonal antibodies Homocysteine EIA ELISA (Axis-Shield Diagnostics Ltd, Scotland), for a period of up to 14 weeks, the subjects were divided into 2 groups: with high concentrations (>10 μmol/L) and normal levels (<10 μmol/L). We controlled complications of pregnancy: loss of pregnancy in the first half, premature birth, delayed fetal growth, congenital malformations of the fetus, gestational hypertension, mild and severe preeclampsia, eclampsia and HELLP syndrome. The results of the study showed that at a level of homocysteine I trimester >10 μmol/l spontaneous abortion, premature birth, gestational hypertension, mild preeclampsia develop more often. There were no differences in the groups for delaying intrauterine growth of the fetus, congenital malformations, severe preeclampsia.
Studies have indicated that thrombophilic genes polymorphisms are associated with recurrent pregnancy loss (RPL) in the Iranian population. We aimed to evaluate the precise association between thrombophilic genes polymorphisms (MTHFR C677T, MTHFR A1298C, Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G) and RPL risk in the Iranian population. PubMed, Web of Science, Google Scholar, and ISC were searched for eligible articles published up to April 1, 2017. In total, 37 case-control studies in 18 relevant publications were selected: 1,199, 1,194, 630, 830, and 955 RPL cases and 1,079, 1079, 594, 794, and 499 controls for MTHFR C677T, MTHFR A1298C,Prothrombin G20210A, FVL G1691A, and PAI-1 4G/5G, respectively. The results indicated a significant increased risk of RPL in all genetic models in the population. Also, Prothrombin G20210A and FVL G1691A as well as PAI-1 4G/5G polymorphisms were associated with RPL risk in the Iranian population. Hence, thrombophilic genes polymorphisms are associated with an increased RPL risk in the Iranian population.
dentify agencies (a person, an organization, or a service) that made contributions to the content or provided funding or support for the work presented in this submission. Separate them with a semi-colon (e.g. John Doe, Metro University; Master University, Department of Computer Science)
Purpose
The aim of this study was to evaluate the role of maternal serum total Homocysteine (tHcy) and uterine artery (Ut-A) Doppler as predictors of preeclampsia (PE), intrauterine growth restriction (IUGR), and other complications related to poor placentation.
Patients and methods
A prospective cohort study was conducted on 500 women with spontaneous pregnancies. tHcy was measured at 15–19 weeks, and then, Ut-A Doppler was performed at 18–22 weeks of pregnancy.
Results
453 pregnant women completed the follow-up of the study. The tHcy and Ut-A resistance index were significantly higher in women who developed PE, IUGR, and other complications when compared to controls (tHcy: 7.033 ± 2.744, 6.321 ± 3.645, and 6.602 ± 2.469 vs 4.701 ± 2.082 μmol/L, respectively, p value <0.001 and Ut-A resistance index: 0.587 ± 0.072, 0.587 ± 0.053, and 0.597 ± 0.069 vs 0.524 ± 0.025, respectively, p value <0.001). The use of both tHcy assessment and Ut-A Doppler improved the sensitivity of prediction of PE relative to the use of each one alone (85.2 relative to 73.33 and 60%, respectively).
Conclusion
The use of elevated homocysteine and uterine artery Doppler screening are valuable in prediction of preeclampsia, IUGR, and poor placentation disorders.
ClincalTrial.gov ID
NCT02854501.
Introduction
The rate of operative birth by Caesarean section is
constantly rising. In Kazakhstan, it reaches 27 per cent.
Research data confirm that the percentage of successful
vaginal births after previous Caesarean section is 50–70 per
cent. How safe the induction of vaginal birth after
Caesarean (VBAC) remains unclear.
Methodology
The studied techniques of labour induction were
amniotomy of the foetal bladder with the vulsellum ramus,
intravaginal administration of E1 prostaglandin
(Misoprostol), and intravenous infusion of Oxytocin-Richter.
The assessment of rediness of parturient canals was
conducted by Bishop’s score; the labour course was
assessed by a partogram. The effectiveness of labour
induction techniques was assessed by the number of
administered doses, the time of onset of regular labour, the
course of labour and the postpartum period and the
presence of complications, and the course of the early
neonatal period, which implied the assessment of the
child’s condition, described in the newborn development
record. The foetus was assessed by medical ultrasound and
antenatal and intranatal cardiotocography (CTG). Obtained
results were analysed with SAS statistical processing
software.
Results
The overall percentage of successful births with intravaginal
administration of Misoprostol was 93 per cent (83) of cases.
This percentage was higher than in the amniotomy group
(relative risk (RR) 11.7) and was similar to the oxytocin
group (RR 0.83). Amniotomy was effective in 54 per cent
(39) of cases, when it induced regular labour. Intravenous
oxytocin infusion was effective in 94 per cent (89) of cases.
This percentage was higher than that with amniotomy (RR
12.5).
Conclusions
The success of vaginal delivery after previous Caesarean
section can be achieved in almost 70 per cent of cases. At
that, labour induction does not decrease this indicator and
remains within population boundaries.
This study aimed to investigate serum methylmalonic acid (MMA) and homocysteine levels and to assess their effects on pregnancy and neonatal outcomes. SerumMMAand homocysteine levels in 278 pregnant Korean women, determined by liquid chromatography–tandem mass spectrometry in each trimester, were compared with those of previous studies in other ethnic groups. We investigated the association between MMA and homocysteine status with pregnancy and neonatal events: gestational diabetes, preeclampsia, gestational age at delivery, preterm birth, small for gestational age, neonatal birth weight, and congenital abnormalities. The median (range) MMA level was 0.142 (0.063–0.446) µmol/L and homocysteine level was 10.6 (4.4–38.0) µmol/L in pregnant women. MMA levels were significantly higher in the third trimester than during other trimesters (p < 0.05), while homocysteine levels were not. No significant association was observed between MMA or homocysteine levels and any of the maternal or neonatal outcomes examined. Future studies are needed to assess the associations among maternal serum concentrations of MMA and homocysteine, and maternal and neonatal outcomes.
Introduction
Increased plasma homocysteine may be associated with adverse pregnancy outcomes, such as preeclampsia. The aim of this study was to determine the plasma homocysteine, serum folate, and vitamin B12 levels in preeclamptic pregnant women.
Methods
This case-control study was conducted in 2016 in Ahwaz on 51 pregnant women with preeclampsia and 51 healthy pregnant women of the same gestational age, who served as controls. The case group also was subdivided into severe and non-severe preeclampsia. Patients’ data were collected through a questionnaire and medical records. Serum homocysteine, folic acid, and vitamin B12 were analyzed using chemiluminescent assay. The results were compared between two groups. Statistical analyses were done using IBM-SPSS 20.0. A Kolmogorov-Smirnov test, independent samples t-test, Mann-Whitney test, and Chi-square test were used for data analysis.
Results
No different demographic characteristics were found among the groups. Pregnant women complicated with preeclampsia displayed significantly higher serum homocysteine levels (p < 0.001) and lower serum folate (p = 0.005) and vitamin B12 levels (p < 0.001) compared to controls. A statistically significant inverse correlation was evident between serum homocysteine and serum folate levels in preeclamptic patients (p = 0.005; r = −0.389). In addition, an inverse correlation was identified between homocysteine and serum vitamin B12, but it was not statistically significant (p = 0.160; r = −0.200). Significant differences occurred in serum homocysteine and folate levels between the severe and non-severe subgroups (p < 0.001, p < 0.001).
Conclusion
Women complicated with preeclampsia displayed higher maternal serum homocysteine and lower serum folate and vitamin B12. Further studies are needed to confirm if the prescription of folic acid and vitamin B12 in women with a deficiency of these vitamins could decrease the level of serum homocysteine and, therefore, reduce the risk of preeclampsia or, if it occurred, its severity.
Homocysteine is a sulfur-containing aminoacid produced during metabolism of methionine. Since 1969 the relationship between altered homocysteine metabolism and both coronary and peripheral atherotrombosis is known; in recent years experimental evidences have shown that elevated plasma levels of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Several mechanisms by which elevated homocysteine impairs vascular function have been proposed, including impairment of endothelial function, production of reactive oxygen species (ROS) and consequent oxidation of low-density lipids. Endothelial function is altered in subjects with hyperhomocysteinemia, and endothelial dysfunction is correlated with plasma levels of homocysteine. Folic acid and B vitamins, required for remethylation of homocysteine to methionine, are the most important dietary determinants of homocysteine and daily supplementation typically lowers plasma homocysteine levels; it is still unclear whether the decreased plasma levels of homocysteine through diet or drugs may be paralleled by a reduction in cardiovascular risk.
Human in utero growth restriction (IUGR) is associated with an increased risk for perinatal mortality and morbidity
among newborns and infants. To pursue this challenge, a Request For Proposals (RFP) was issued in 1983
by The U.S. Epidemiology and Biometry Research Program at the National Institute of Child Health and Human
Development (NICHD). A consortium was set up at the universities and university hospitals in Trondheim,
Bergen (Norway) and Uppsala (Sweden) and was funded by the NICHD to conduct the Scandinavian Successive
Small-for-Gestational Age (SGA) pregnancy and birth outcome study . The study design included a comprehensive
biobank with maternal and cord serum samples, placental tissue, and a multitude of data collected from
interviews, questionnaires, and clinical examinations.
The SGA cohort study involved 6,354 Caucasian pregnant women in the three study sites who expected their
second or third child from 1986-88. The study women were screened in early second trimester and mothers who
had an increased risk to deliver a smaller than expected newborn were followed in detail through the second half
of pregnancy and at birth. Selected children were screened several times through their first and up to five years
of age. Moreover, a highly selected subgroup in Trondheim has been followed at 14, 19, and 26 years’ age.
Almost thirty years later, we have searched the body of scientific publications that originated from this cohort
study in an attempt to assess if and to what extent the main aims and objectives were achieved and to summarize
the overall outcomes. The SGA cohort has resulted in close to 100 published papers in peer reviewed journals
and some 40 graduate and undergraduate degrees. Risk factors of SGA, like maternal smoking, low prepregnancy
weight and education attainment, and a previous SGA birth outcome were confirmed. Conversely, no
totally new and unknown risk factors were identified. Serial ultrasound measures have enabled a distinction
between SGA with restricted and normal intrauterine growth, and has further indicated that being born SGA is
mainly a problem in combination with IUGR. Further, the consequences of IUGR are more pronounced at
adolescence and young adulthood than at five years of age.
An increased understanding of the pathogenesis of different categories of growth restriction is essential to
recognize and diagnose IUGR properly, and to reduce the perinatal mortality and morbidity from SGA. Moreover,
SGA is a significant predictor at follow-up of the child. An up to date biobank has ensured the quality of data
and biological samples, and has been crucial for the outcome of the entire SGA study. It continues to be a
valuable resource in future research.
Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia.
We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early-onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis.
There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only.
Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients.
Hypertensive disorders of pregnancy contribute significantly to maternal mortality and morbidity. Preeclampsia belongs to the spectrum of hypertensive disorders of pregnancy and if undiagnosed and/or untreated leads to fatal consequences for both the mother and the baby. Early detection and prevention of preeclampsia is limited by uncertainty in the knowledge about its etiopathogenesis. While much work has been done in establishing clinical guidelines for management of preeclampsia in the hospital or tertiary care settings, there is considerable lack of work in the domain of evidence-based guidelines for screening, identification and management of preeclampsia at the community-level. The article reviews these issues with special considerations and to challenges faced in low and middle-income countries. There is a need to focus on low-cost screening and interventions in the community to achieve a significant impact on preventable maternal and fetal mortality in order to control the burden of preeclampsia significantly as well as investing on more research at primary care level to improve the evidence base for community-level interventions.
Objectives: Pre-eclampsia affects approximately 5-8% of pregnant women. The aim of this study was to compare the serum level of Lactate dehydrogenase (LDH), Homocystein, Hemoglubin and platelet in pregnant women diagnosed as pre-eclampsia and a normal group in Gorgan city, Northeastern Iran from 2007-2008. Methodology: In this case control study, 50 cases of pre-eclampsia were compared with the control group women hospitalized in Dezyani hospital. Pre-eclampsia criteria were: Blood pressure more than or equal to 140/90 mm hg and Proteinuria greater or equal to 300 mg/ 24 hours urine sample in the third trimester. Hemoglobin, platelet, LDH and hemocystein were measured. Data were analyzed by the mean of SPSS-14 program & Chi-2 or t-student were used. Results: The difference of BMI and family incomes was significant between two groups (P-value<0.01). LDH level was not statistically different between healthy and pre-eclamptic individuals. Six cases (12%) in controls and 9 cases (18%) in pre-eclamptic group had thrombocytopenia (P-value>0.01). Hemocystein level was more than normal range in five patients with pre-eclampsia (P-value<0.001). Conclusions: In this study, hemocystein level was significantly higher in pre-eclampsia patients but LDH, hemoglobin and platelet level had no significant difference.
Purpose
Recurrent
pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses before the 20th week of gestation with the same partner. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms were reported to have an effect on embryonic development and pregnancy success. To clarify the effects of MTHFR polymorphisms on the risk of RPL in the Chinese population, a meta-analysis was performed.
Materials and methods
Related studies were identified from Medline, Embase, Web of Science, and Chinese Databases up to March 7th, 2015. We extracted the number of both C677T and A1298C genotypes in the cases and controls. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to estimate the associations. Data analysis was performed using Stata 13.1.
Results
Sixteen articles involving 1420 RPL cases and 1408 controls were included in this meta-analysis. MTHFR C677T polymorphism was significantly associated with RPL risk under dominant (TT + CT vs. CC; OR 2.10, 95 % CI 1.76–2.50), recessive (TT vs. CC + CT; OR 2.36, 95 % CI 1.92–2.90), heterozygote (CT vs. CC; OR 1.77, 95 % CI 1.32–2.37), homozygote (TT vs. CC; OR 3.55, 95 % CI 2.76–4.56), and additive (T vs. C; OR 1.83, 95 % CI 1.64–2.05) model. Sensitivity analyses excluding studies that deviated from HWE did not change the direction of effect. For the A1298C mutation, no significant association was found. The Egger’s regression asymmetry test showed no significant publication bias.
Conclusions
Identification of MTHFR C677T mutation would have some implication for primary prevention of RPL and screening of high-risk individuals in China. Large well-designed researches are needed to fully describe the associations.
Objective: The aim of this study was to analyze homocysteine levels in maternal serum in women with pregnancies complicated by preeclampsia and/or IUGR. Patients and methods: The study was carried out on 49 pregnant patients with normotensive pregnancies complicated by intrauterine fetal growth restriction (group IUGR), 31 patients with preeclampsia complicated by IUGR (group PRE-IUGR), and 35 preeclamptic patients with appropriate-for-gestational-age weight fetuses (group PRE). The control group consisted of 47 healthy normotensive pregnant patients with singleton uncomplicated pregnancies and with proper intrauterine fetal growth. Results: We revealed higher levels of maternal serum homocysteine in the group of pregnant patients with isolated fetal intrauterine growth restriction in comparison with the control subjects. The concentrations of homocysteine were also higher in both groups of patients with pregnancy complicated by preeclampsia with and without IUGR. The highest levels of homocysteine were observed in preeclamptic women with appropriate-for-gestational-age fetal growth. The mean values were 9.004 +/– 2.820 umol/L in the IUGR group, 10.815 +/– 3.785 umol/ L in the group PRE, 9.808 +/– 2.543 umol/L in the group PRE-IUGR and 7.639 +/– 2.728 umol/L in the control group. Conclusions: Increased levels of homocysteine are involved in pathogenesis IUGR and preeclampsia and may contribute to endothelial cells activation or dysfunction observed in these pregnancy disorders. Further studies are needed to explain these aspects in order to improve the management and therapeutic strategies for pregnancies complicated by IUGR and/or preeclampsia.
To investigate the incidence and high-risk factors of fetal growth restriction (FGR) in Mainland China and determine the adverse effects of this condition on fetal-neonatal health.
This study was a retrospective chart review. We investigated the incidence rate of FGR using a retrospective analysis of clinical data obtained from mothers and newborns from 7 hospitals in Mainland China from January 1 to December 31, 2011. The short-term outcomes of FGR were analyzed based on data obtained from the neonatal intensive-care unit (NICU) of Bayi Children's Hospital. The long-term outcomes of FGR were determined after a follow-up study of 125 cases of FGR in children at 18 months. The physical development index, mental development index (MDI), and psychomotor development index (PDI) were compared between FGR patients and controls.
The incidence of FGR was 8.77%. The incidence of FGR was significantly higher in females than in males (9.80% vs 7.84%, P < 0.05). The incidence of FGR in preterm infants was higher than that in full-term infants (16.43% vs 7.87%, P < 0.01). Chronic hypertension, abnormal amniotic fluid, and umbilical cord abnormalities were independent factors of FGR. A significantly higher incidence of complications, including hypoglycemia, asphyxia, hypoxic-ischemic encephalopathy, gastrointestinal bleeding, congenital malformations, polycythemia, lung hemorrhage, apnea, congenital heart disease, and disseminated intravascular coagulation, was observed in FGR patients than in controls. The FGR prolonged the duration of the hospital stay and markedly increased hospitalization expenses (P < 0.05). Children with FGR showed catch-up growth, which reached the level of the control group after 1.5 years, but these individuals still had lower MDI and PDI scores.
The incidence rate of FGR in Mainland China was 8.77%. It has a significantly adverse effect on fetal-neonatal health and cognitive development.
Aim. To revisit the role of first trimester homocysteine levels with the maternal and fetal outcome. Methods. This was a cohort study comprising 100 antenatal women between 8 and 12 weeks of gestation. Serum homocysteine levels were checked after overnight fasting. Results. There were significantly elevated homocysteine levels among women with prior history of hypertensive disorders of pregnancy and prior second or third trimester pregnancy losses. There was no significant difference in homocysteine levels among women with previous gestational diabetes mellitus, preterm deliveries, or fetal malformations. Homocysteine levels were significantly elevated in those who developed hypertensive disorder of pregnancy, oligohydramnios, and meconium stained amniotic fluid, had a pregnancy loss, or delivered a low birth weight baby. There was no significant difference in homocysteine levels for those who developed gestational diabetes mellitus. Conclusions. Increased first trimester serum homocysteine is associated with history of pregnancy losses, hypertensive disorders of pregnancy, and preterm birth. This is also associated with hypertensive disorders of pregnancy, pregnancy loss, oligohydramnios, meconium stained amniotic fluid, and low birth weight in the current pregnancy. This trial is registered with ClinicalTrials.gov CTRI/2013/02/003441.
Background
The aim of this study was to determine the maternal serum concentrations of eNOS, ADMA, and homocysteine in preeclamptic pregnancies.
Material/Methods
The study was carried out on 62 patients with pregnancy complicated by early onset and 53 patients with late onset preeclampsia. The control group consisted of 65 healthy normotensive pregnant patients. The serum eNOS, ADMA and homocysteine concentrations were determined using ELISA assays.
Results
Our study revealed elevated levels of homocysteine and ADMA in the serum of women with preeclampsia. The highest levels were observed in patients with early onset preeclampsia, but the differences between both groups of preeclamptic patients with early and late onset of preeclampsia were not statistically significant. Both groups of preeclamptic women had slightly lower levels of maternal serum endothelial nitric oxide synthase than in normotensive pregnant women, but these differences were not statistically significant.
Conclusions
The higher levels of homocysteine and ADMA observed in patients with early onset preeclampsia may suggest that higher levels of maternal serum homocysteine and ADMA correlate with the severity, and may determine the earlier clinical onset of the disease. The elevated levels of ADMA and the unchanged levels of eNOS in preeclamptic pregnancies suggest that NO deficiency in this pregnancy disorder results not from a reduced level or activity of eNOS, but from elevated levels of ADMA, an endogenous eNOS inhibitor. The lowering of increased levels of homocysteine and ADMA may be helpful in therapy of vascular disturbances occurring in preeclampsia.
There is increasing evidence that pre-eclampsia, a principal cause of maternal morbidity, may also be a risk factor for future cardiovascular and cerebrovascular events. This review aimed to assess the current evidence and quantify the risks of cardiovascular disease (CVD), cerebrovascular events and hypertension associated with prior diagnosis of pre-eclampsia. Medline and Embase were searched with no language restrictions, as were core journals and reference lists from reviews up until January 2012. Case-control and cohort studies which reported cardiovascular and cerebrovascular diseases or hypertension diagnosed more than 6 weeks postpartum, in women who had a history of pre-eclampsia relative to women who had unaffected pregnancies, were included. Fifty articles were included in the systematic review and 43 in the meta-analysis. Women with a history of pre-eclampsia or eclampsia were at significantly increased odds of fatal or diagnosed CVD [odds ratio (OR) = 2.28, 95 % confidence interval (CI): 1.87, 2.78], cerebrovascular disease (OR = 1.76, 95 % CI 1.43, 2.21) and hypertension [relative risk (RR) = 3.13, 95 % CI 2.51, 3.89]. Among pre-eclamptic women, pre-term delivery was not associated with an increased risk of a future cardiovascular event (RR = 1.32, 95 % CI 0.79, 2.22). Women diagnosed with pre-eclampsia are at increased risk of future cardiovascular or cerebrovascular events, with an estimated doubling of odds compared to unaffected women. This has implications for the follow-up of all women who experience pre-eclampsia, not just those who deliver pre-term. This association may reflect shared common risk factors for both pre-eclampsia and cardiovascular and cerebrovascular disease.
Hepatic steatosis is common in patients having severe hyperhomocysteinemia due to deficiency for cystathionine beta-synthase. However, the mechanism by which homocysteine promotes the development and progression of hepatic steatosis is unknown. We report here that homocysteine-induced endoplasmic reticulum (ER) stress activates both the unfolded protein response and the sterol regulatory element-binding proteins (SREBPs) in cultured human hepatocytes as well as vascular endothelial and aortic smooth muscle cells. Activation of the SREBPs is associated with increased expression of genes responsible for cholesterol/triglyceride biosynthesis and uptake and with intracellular accumulation of cholesterol. Homocysteine-induced gene expression was inhibited by overexpression of the ER chaperone, GRP78/BiP, thus demonstrating a direct role of ER stress in the activation of cholesterol/triglyceride biosynthesis. Consistent with these in vitro findings, cholesterol and triglycerides were significantly elevated in the livers, but not plasmas, of mice having diet-induced hyperhomocysteinemia. This effect was not due to impaired hepatic export of lipids because secretion of VLDL-triglyceride was increased in hyperhomocysteinemic mice. These findings suggest a mechanism by which homocysteine-induced ER stress causes dysregulation of the endogenous sterol response pathway, leading to increased hepatic biosynthesis and uptake of cholesterol and triglycerides. Furthermore, this mechanism likely explains the development and progression of hepatic steatosis and possibly atherosclerotic lesions observed in hyperhomocysteinemia.
Growth retardation in utero leading to small-for-gestational-age (SGA) newborns is associated with increased neonatal morbidity and mortality and with lifelong consequences such as poor cognitive function and cardiovascular diseases. Maternal total homocysteine (tHcy) concentrations have been linked to a wide range of adverse pregnancy outcomes and could possibly influence birth weight.
We performed a systematic review of and meta-analysis on the association of maternal tHcy and birth weight.
A literature search of English, German, and French publications with the use of the PubMed database (January 1966-July 2010) found 78 abstracts. Search terms were as follows: homocysteine AND (birth weight OR small for gestational age OR intrauterine growth retardation). Studies were eligible if information on maternal tHcy and birth weight and the possible association between maternal tHcy and birth weight was available. Effect size estimates were converted to ORs as estimates of the RR of a woman to deliver SGA offspring when maternal tHcy exceeded the 90th percentile.
The search yielded 19 studies for analysis, consisting of 21,326 individuals. Pooled analysis resulted in a crude OR of 1.25 (95% CI: 1.09, 1.44). When this estimate was expressed as a linear effect, it corresponded to a decrease in birth weight of 31 g (95% CI: -13, -51 g) for a 1-SD increase in maternal tHcy.
Higher maternal tHcy concentrations are associated with a small increased risk for SGA offspring. The small estimated birth weight difference might be of little clinical relevance for the individual newborn; however, it could be of greater importance at a population level.
Our aim in this study was to investigate the association between elevated homocysteine levels and the two MTHFR polymorphisms, C677T and A1298C, with several pregnancy complications such as recurrent pregnancy loss, preeclampsia, placental abruption and intrauterine growth retardation. In 203 women with different placental vasculopathies, we determined the MTHFR C677T and the A1298C prevalence and their relative association to elevated homocysteine levels. The mean plasma homocysteine level was significantly higher in the pathologic groups when compared with the control group. We identified the carriage of the MTHFR A1298C polymorphism as a significant risk factor for vascular-related pregnancy complications. Women with MTHFR A1298C polymorphism or elevated homocysteine levels have an increased risk of placental vasculopathies. The MTHFR A1298C mutation also had a positive impact on elevated homocysteine levels. The lack of association between the MTHFR C677T polymorphism and pregnancy morbidities needs further studies.
This overview addresses homocysteine and folate metabolism. Its functions and complexity are described, leading to explanations why disturbed homocysteine and folate metabolism is implicated in many different diseases, including congenital birth defects like congenital heart disease, cleft lip and palate, late pregnancy complications, different kinds of neurodegenerative and psychiatric diseases, osteoporosis and cancer. In addition, the inborn errors leading to hyperhomocysteinemia and homocystinuria are described. These extreme human hyperhomocysteinemia models provide knowledge about which part of the homocysteine and folate pathways are linked to which disease. For example, the very high risk for arterial and venous occlusive disease in patients with severe hyperhomocysteinemia irrespective of the location of the defect in remethylation or transsulphuration indicates that homocysteine itself or one of its "direct" derivatives is considered toxic for the cardiovascular system. Finally, common diseases associated with elevated homocysteine are discussed with the focus on cardiovascular disease and neural tube defects.
Elevated blood levels of homocysteine are associated with atherosclerosis and thrombotic disease. We previously reported that treatment of cultured endothelial cells with homocysteine increased endogenous factor V activity by activation of the cofactor. Because endothelial cell-associated factor Va would be regulated by the protein C mechanism, the ability of homocysteine-treated arterial and venous endothelial cells to activate protein C was investigated. Both arterial and venous endothelial cells activated protein C; 0.6 mmol/L homocysteine reduced endothelial cell protein C activation by 12%. Maximal inhibition (90%) of protein C activation occurred with 7.5 to 10 mmol/L homocysteine after 6 to 9 hours of incubation. Metabolism of homocysteine was not accelerated by cultured endothelial cells. Investigation of the mechanism(s) by which homocysteine reduced protein C activation indicated that the metabolite did not induce an inhibitor to activated protein C, but in low concentrations acted as a competitive inhibitor to thrombin. These data suggest that perturbation of the vascular endothelial cell protein C mechanism by homocysteine may contribute to the thrombotic tendency seen in patients with elevated blood levels of this metabolite.
Thrombomodulin plays a role as a cofactor for thrombin-catalyzed activation of protein C on endothelial cells. We examined the effect of homocysteine, a stimulant of atherosclerosis and thrombotic disease, on the cofactor activity and protein level of thrombomodulin and also on the expression of thrombomodulin in endothelial cells. Homocysteine inhibited the cofactor activity of thrombomodulin both on the surface of endothelial cells and in the whole cells dose- and time-dependently, and maximal inhibition of the cofactor activity occurred after a 3- to 6-hour incubation with 10 mmol/L homocysteine (10% of initial activity). Homocysteine also decreased the amount of intact (unreduced) thrombomodulin in endothelial cells. However, at the same condition the total protein level (reduced and unreduced form) of thrombomodulin, determined by dot immunoblot analysis using the monoclonal antibody that recognized both reduced and unreduced thrombomodulin, decreased slightly, and the mRNA level of thrombomodulin showed a twofold to three-fold increase. After 24 hours of incubation, the cofactor activity and total protein level of thrombomodulin were 60% and 165% of the initial values, respectively. When purified thrombomodulin fixed to a microwell plate was treated with homocysteine, both cofactor activity and thrombin-binding ability to the thrombomodulin were decreased in proportion to the concentration of homocysteine. These findings suggest that homocysteine directly inhibited the cofactor activity of thrombomodulin on endothelial cells by reducing the disulfide-bond rich epidermal growth factor-like structures of thrombomodulin. This would a result in the decrease of the antithrombotic property of endothelium and may also trigger off the synthesis of mRNA and protein of thrombomodulin to maintain the antithrombotic properties of the cells.
Background: Total homocysteine (tHcy) measured in serum or plasma is a marker of folate status and a risk factor for cardiovascular disease.
Objective: Our objective was to investigate associations between tHcy and complications and adverse outcomes of pregnancy.
Design: Plasma tHcy values measured in 1992–1993 in 5883 women aged 40–42 y were compared with outcomes and complications of 14492 pregnancies in the same women that were reported to the Medical Birth Registry of Norway from 1967 to 1996.
Results: When we compared the upper with the lower quartile of plasma tHcy, the adjusted risk for preeclampsia was 32% higher [odds ratio (OR): 1.32; 95% CI: 0.98, 1.77; P for trend = 0.02], that for prematurity was 38% higher (OR: 1.38; 95% CI: 1.09, 1.75; P for trend = 0.005), and that for very low birth weight was 101% higher (OR: 2.01; 95% CI: 1.23, 3.27; P for trend = 0.003). These associations were stronger during the years closest to the tHcy determination (1980–1996), when there was also a significant relation between tHcy concentration and stillbirth (OR: 2.03; 95% CI: 0.98, 4.21; P for trend = 0.02). Neural tube defects and clubfoot had significant associations with plasma tHcy. Placental abruption had no relation with tHcy quartile, but the adjusted OR when tHcy concentrations >15 μmol/L were compared with lower values was 3.13 (95% CI: 1.63, 6.03; P = 0.001).
Conclusion: Elevated tHcy concentration is associated with common pregnancy complications and adverse pregnancy outcomes.
Objective:
To investigate the change of level of serum homocysteine (Hcy), endothelin-1 (ET-1) and nitric oxide (NO) and clinical significance in patients with HDCP.
Methods:
Two hundred and thirty nine patients with HDCP (137 patients with mild preeclampsia, 102 patients with severe preeclampsia) who were hospitalized between June 2012 and June 2015 and 200 normal pregnancy women in outpatient department were enrolled in our study were divided into HDCP group and control group. Serum Hcy concentration was measured by enzymatic cycling assay. ET-1 concentration was measured by enzyme linked immunosorbent assay. And no concentration was measured by nitrate reductase assay.
Results:
Serum Hcy and ET-1 in HDCP group were significantly higher as compared to control group (P<0.05). Level of serum NO in HDCP group was significantly lower than in the control group (P<0.05). Level of serum Hcy and ET-1 in mild and severe preeclampsia group were significantly higher as compared to control group, respectively (P<0.05). Level of serum NO in mild and severe preeclampsia group were significantly lower than in the control group' respectively (P<0.05). Level of serum Hcy and ET-1 in severe preeclampsia group were significantly higher as compared to mild preclampsia group (P<0.05). Level of serum NO in severe preeclampsia group were significantly lower than in mild preeclampsia group (P<0.05). Spearman rank correlation analysis showed that level of serum Hcy and ET-1 was positively correlated with severity of diseases (r=0.689, 0.718, P<0.05). Level of serum NO was negatively correlated with severity of diseases (r=-0.702, P<0.05).
Conclusion:
Serum Hcy, ET-1 and NO were associated with pathogenesis of HDCP. Comprehensively measurement of them could effectively evaluate the incidence and progress of HDCP.
