Search Results (77)

Background and Objectives: Calcium is an essential mineral that plays a vital role in fetal development and maternal health during pregnancy. The World Health Organization recommends a daily calcium intake of 1.5–2 g for pregnant adult women. Calcium deficiency during gestation may lead to complications, such as gestational hypertension, preeclampsia, loss of bone mineral density, impaired fetal development, and other adverse pregnancy outcomes. The aim of the present review is to evaluate the current clinical evidence on calcium intake during pregnancy. Methods: The present systematic review was conducted according to the PRISMA 2020 statement by searching two major databases, PubMed and Mendeley. The study protocol was registered in the Open Science Framework (DOI: osf.io/rvj7z). Inclusion criteria were clinical trials on calcium supplementation during pregnancy. Exclusion criteria were clinical guidelines, reviews, case reports, case series, letters, and commentaries. The Newcastle–Ottawa Scale was used to assess the risk of bias in the included studies. Results: Initially, 451 publications were identified, and after removal of duplicates and screening of titles and/or abstracts and/or full texts, 34 studies were included. The number of participants ranged between 30 and 22,000 women. Calcium supplementation was associated with lower incidence of and less severe gestational hypertension and preeclampsia, lower risk of preterm birth, longer pregnancy duration and higher neonatal birth weight, and improved maternal bone mineral density postpartum. When the doses were split up into smaller doses, the benefits were strongest with high-dose regimens (1.5–2 g/day). Conclusions: Calcium supplementation during pregnancy has beneficial effects on maternal and neonatal health, especially in populations with insufficient dietary daily calcium intake and women at high risk of hypertensive disorders. Daily dose may vary according to individual needs, daily dietary calcium intake, and general health status. Further large-scale randomized controlled trials (RCTs) are necessary to confirm these findings. Full article

Background/Objectives: Preeclampsia (PE), characterized by its complex and multisystemic nature, significantly compromises the health outcomes of both mothers and their newborns. According to recent research, its underlying pathophysiological mechanisms may be influenced by abnormalities in lipid metabolism. The purpose of this study is to assess the association between unfavorable pregnancy outcomes and increased lipoprotein(a) levels in the first trimester and the subsequent risk of PE. Methods: A prospective cohort study comprising 150 pregnant women with a gestational age of less than 12 weeks and no history of PE was carried out at the University Hospital of Ioannina. In the first trimester, lipoprotein(a) levels were assessed, and individuals were monitored for the emergence of preeclampsia, preterm birth, gestational hypertension without proteinuria, and fetal growth limitation. Selection bias was minimized through the use of sequential sampling and rigorous inclusion and exclusion criteria. Associations were assessed using logistic regression analysis. Results: Women with elevated lipoprotein(a) levels had a considerably greater risk of PE than those with normal levels (64.7% vs. 15.5%, p < 0.001). Additionally, elevated lipoprotein(a) was linked to higher odds of fetal growth restriction (p < 0.001), gestational hypertension without proteinuria (p = 0.024), and premature delivery (p = 0.009). These results imply that early lipoprotein(a) screening during pregnancy may help identify women who are at high risk for PE and its associated negative consequences. Conclusions: The association between PE and elevated first-trimester lipoprotein(a) levels highlights the necessity for a deeper understanding of the underlying pathophysiological mechanisms, which could ultimately improve outcomes for both mothers and newborns. Full article

Background: Pregnancy simulates a metabolic syndrome-like state and predisposes to iodine deficiency and hypothyroidism through increased iodine renal loss and transplacental transfer to the fetus. Iodine deficiency is thought to predispose to dyslipidemia through elevation of serum TSH. Obesity, dyslipidemia, and hypothyroidism are established risk factors of preeclampsia. Hence, pregnant women with iodine deficiency are likely to be at increased risk of dyslipidemia and preeclampsia. We investigated the pattern of dyslipidemia among preeclamptic and normotensive pregnant women with and without iodine deficiency. Methods: The pathophysiological mechanisms linking iodine deficiency and dyslipidemia were delineated using bivariate correlations, logistic regression, and exploratory factor analysis of anthropometric, lipid profile, urine iodine concentration (UIC), and thyroid function data from 240 women with preeclampsia and 120 normotensive pregnant controls at term who attended Lomo Medical Centre, Democratic Republic of Congo (DRC). Results: Preeclamptic women with iodine deficiency had significantly lower HDL-C but higher triglyceride levels than those with sufficient iodine intake. Both normotensive and preeclamptic participants with elevated TSH had high serum oxidized LDL-C but low NO, p < 0.001. Conclusions: SCH, secondary to iodine deficiency, is associated with elevated serum oxidized LDL and decreased Nitric Oxide (NO) among both normotensive and preeclamptic women, while insufficient iodine nutrition among preeclamptic women predisposes to reduced HDL-C and increased serum Triglycerides, which are risk factors of atherosclerosis and cardiovascular disease. Full article

Background and Objectives: Several micro- and macro-nutrient malnutrition states that are routinely assessed during clinical care of women in the antenatal period have been proposed as risk factors for preeclampsia. However, there is a paucity of data on the potential use of these biomarkers for detection of preeclampsia. The aim of this case-control study was to investigate the association of biomarkers from routine clinical tests, and those specific to micro- and macro-nutrient malnutrition, with the risk of preeclampsia. Materials and Methods: Venous blood samples of 250 participants with preeclampsia and 150 pregnant women without preeclampsia were collected and assayed immediately for the full blood count, urea and electrolytes, high-density cholesterol (HDL), total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), oxidized low-density lipoprotein cholesterol (OxLDL), and selenium, in addition to urine iodine concentration (UIC). Results: The serum potassium/magnesium ratio (K⁺/Mg²⁺), UIC, fasting plasma glucose (FPG), thyroid stimulating hormone (TSH), lymphocyte percentage (L/WBC%), and the oxidized LDL/albumin ratio (OxLDL/Alb) were identified as independent predictors of preeclampsia. Conclusions: Serum potassium/magnesium ratio and other analytes essential for various biological processes, some of which are assayed during routine care, were significantly associated with preeclampsia, warranting further exploration as potential screening biomarkers in low-resource settings. Full article

Pre-eclampsia (PE) affects about 5% of all pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality. Some reports suggest that micronutrients may influence this condition, but there is no existing report analyzing data on copper (Cu), selenium (Se), and zinc (Zn) regarding quality and bias. Accurate information is crucial to support governmental healthcare actions, especially in developing countries such as Brazil. This study aims to investigate whether alterations in Zn, Cu, and Se levels in pregnant women contribute to the development of PE. We conducted the study following PRISMA guidelines and registered it on PROSPERO (CRD42022302298). We searched LILACS, PubMed/MEDLINE, EMBASE, and the Cochrane Library databases from January 2000 to January 2024. Of 1202 reports, 42 manuscripts were suitable for analysis (contained one or more micronutrients). A total of 76 individual analyses (by nutrient) were performed using Joanna Briggs Critical Appraisal and Cochrane Risk of Bias Tools. The analyses classified 69 reports as fair/low-quality with bias. Due to this, a meta-analysis was not conducted, as the results would not have accurately reflected reality. Of the high-quality reports, five on Cu showed conflicting results, while two studies on Zn found no differences in the level of this micronutrient between normal and PE pregnancies. No high-quality studies were identified for Se. The results highlight the need for robust guidelines for research involving micronutrients and PE to address this question effectively. Full article

Even in the highest inhabited regions of the world, well above 2500 m altitude, women become pregnant and give birth to healthy children. The underlying adaptation to hypobaric hypoxia provides interesting insights into the physio(patho)logy of the human placenta. Although increasing altitude is regularly associated with fetal growth restriction (FGR), oxygen deficiency does not appear to be a direct cause. Rather, placental oxygen consumption is reduced to maintain the oxygen supply to the fetus. This comes at the expense of placental synthesis and transport functions, resulting in inappropriate nutrient supply. The hypoxia-inducible factor (HIF-1α), which modulates the mitochondrial electron transport chain to protect placental tissue from reactive oxygen species, plays a key role here. Reduced oxygen consumption also reflects decreased placental vascularization and perfusion, which is accompanied by an increased risk of maternal pre-eclampsia at high altitude. In native highlanders, the latter seems to be attenuated, partly due to a lower release of HIF-1α. In addition, metabolic peculiarities have been described in indigenous people that enhance glucose availability and thus reduce the extent of FGR. This review attempts to revisit the (albeit incomplete) knowledge in this area to draw the clinical reader’s attention to the crucial role of the placenta in defending the fetus against hypoxia. Full article

Background: Preeclampsia, affecting 2–4% of pregnancies worldwide, poses a substantial risk to maternal health. Late-onset preeclampsia, in particular, has a high incidence among preeclampsia cases. However, existing prediction models are limited in terms of the early detection capabilities and often rely on costly and less accessible indicators, making them less applicable in resource-limited settings. Objective: To develop and evaluate prediction models for late-onset preeclampsia using general information, maternal risk factors, and laboratory indicators from early gestation (6–13 weeks). Methods: A dataset of 2000 pregnancies, including 110 late-onset preeclampsia cases, was analyzed. General information and maternal risk factors were collected from the hospital information system. Relevant laboratory indicators between 6 and 13 weeks of gestation were examined. Logistic regression was used as the baseline model to assess the predictive performance of the support vector machine and extreme gradient boosting models for late-onset preeclampsia. Results: The logistic regression model, only considering general information and risk factors, identified 19.1% of cases, with a false positive rate of 0.4%. When selecting 15 factors encompassing general information, risk factors, and laboratory indicators, the false positive rate increased to 0.7% and the detection rate improved to 27.3%. The support vector machine model, only considering general information and risk factors, achieved a detection rate of 27.3%, with a false positive rate of 0.0%. After including all the laboratory indicators, the false positive rate increased to 7.7% but the detection rate significantly improved to 54.5%. The extreme gradient boosting model, only considering general information and risk factors, achieved a detection rate of 31.6%, with a false positive rate of 1.5%. After including all the laboratory indicators, the false positive rate remained at 0.7% but the detection rate increased to 52.6%. Additionally, after adding the laboratory indicators, the areas under the ROC curve for the logistic regression, support vector machine, and extreme gradient boosting models were 0.877, 0.839, and 0.842, respectively. Conclusion: Compared with the logistic regression model, both the support vector machine and extreme gradient boosting models significantly improved the detection rates for late-onset preeclampsia. However, the support vector machine model had a comparatively higher false positive rate. Notably, the logistic regression and extreme gradient boosting models exhibited high negative predictive values of 99.3%, underscoring their effectiveness in accurately identifying pregnant women less likely to develop late-onset preeclampsia. Additionally, logistic regression showed the highest areas under the ROC curve, suggesting that the traditional model has unique advantages in relation to prediction. Full article

Neurofibromatosis is a genetic disorder arising de novo or with an autosomal dominant transmission that typically presents either at birth or in early childhood, manifesting through distinctive clinical features such as multiple café-au-lait spots, benign tumors in the skin, bone enlargement, and deformities. This literature review aims to resume the spectrum of maternal and fetal complications encountered in pregnant women with neurofibromatosis type 1 (NF1). Thorough research was conducted on databases such as Web of Science, PubMed, Science Direct, Google Scholar, and Wiley Online Library. This review includes 48 case reports, original studies, and reviews on NF1 in pregnancy. The research on the interlink between NF1 and fertility and its influence on human-assisted reproduction techniques is limited. Preimplantation testing (by in vitro fertilization) and prenatal diagnosis (by chorionic villus sampling or amniocentesis) are available to detect affected fetuses. However, genotype–phenotype correlation is difficult to predict. Preconceptional planning and targeted investigations are crucial in understanding the extent of maternal disease. Although in some cases lesions can evolve rapidly during pregnancy, most pregnancies and births in NF1 go well with careful planning. There is a higher incidence of pheochromocytomas and pre-eclampsia, vascular rupture, and cardio-respiratory issues. Anesthesia at birth is a challenge in most cases, and before offering spinal anesthesia, imaging tests should be performed to characterize spinal lesions. General anesthesia may also be challenging when the disease affects the face, neck, upper spine, or airways. Birth-related difficulties may arise because of large neurofibromas located at the level of skin incision or birth canal; uterine atony may be expected if there are uterine lesions. Some complications can develop in postpartum, and affected women should be carefully followed even after pregnancy. Fetal risks include preterm birth (spontaneous or iatrogenic), growth restriction and developmental issues, birth complications, cardiovascular risk, and fetal/neonatal demise. Pregnancies in women with NF1 should be regarded as high-risk and followed in a multidisciplinary fashion. Careful assessment of lesions is of utmost importance before and during pregnancy for anticipating potential maternal risks and before birth to plan anesthesia and delivery. Full article

Background/Objectives: Zika disease is caused by the Zika virus (ZIKV) and represents a major public health problem because of the complications in newborn babies from mothers who were infected during pregnancy. It is estimated that 80% of infected pregnant women are asymptomatic, which complicates the identification of infected individuals. In this study, we aimed to detect ZIKV in asymptomatic pregnant women and the effects in the newborns were analyzed. Methods: The presence of ZIKV was evaluated through endpoint reverse transcription–polymerase chain reaction (RT-PCR) in 114 blood samples from pregnant women treated at two hospitals in the state of Veracruz, Mexico. There was a follow-up of the participants until the birth of their newborns. Results: ZIKV RNA was detected in 4.4% (n = 5) of cases. In two positive cases, two consecutive samples were obtained, and one case of persistence of ZIKV in serum after 90 days after delivery was identified. A total of 80% of the positive cases were identified after the third trimester of pregnancy and 20% after the second trimester. Although ZIKV was shown to be a risk factor for low weight and low size at birth and prematurity, after adjustment for other variables, it did not show a significant association. In contrast, preeclampsia/eclampsia was identified as a significant risk factor for low birth weight. Conclusions: The prevalence of ZIKV found in this study suggests a latent circulation of this virus and highlights the importance of epidemiological surveillance in endemic zones. The prolonged viremia that was found suggests the need for more research because of the high impact which can mean the possible dissemination of the virus to the vector. Full article

Background: Pregnant women with congenital heart disease carry a high risk of complications, especially when cardiac function is suboptimal. Increasing evidence suggests that impaired right ventricular (RV) function has a negative effect on placental function, possibly through venous congestion. We report a case series of hepatic and renal venous flow patterns in pregnant women with right ventricular dysfunction after repaired Tetralogy of Fallot (ToF), relative to those observed in normal pregnancy and preeclampsia. Methods: At 20–24 weeks pregnancy, RV function was measured by echocardiography and by cardiovascular magnetic resonance in women with repaired ToF. Combined Doppler-ECG of the hepatic and renal interlobular veins were performed in three women with asymptomatic right ventricular dysfunction. Venous impedance index and pulse transit time were measured and classified as abnormal at >75th and <25th reference percentile, respectively. Results: All three women showed dilated RV and mildly impaired RV function. Both hepatic and intrarenal Doppler flow waves were abnormal and very much resembled the patterns seen in preeclampsia. One of the three women had complications including ventricular tachycardia, intrauterine growth restriction, antenatal bleeding, emergency cesarean section and acute heart failure 2 days postpartum. Conclusions: Pregnant women with mild right ventricular dysfunction after repaired ToF show abnormal venous Doppler flow waves in the liver and kidneys, similar to those observed in preeclampsia. These findings are in line with reported observations on the association between impaired RV function, abnormal return of venous blood, venous congestion and organ dysfunction. The parallel with venous Doppler flow observations in preeclampsia suggest that the venous compartment might play an important role in the etiology of preeclampsia-induced organ dysfunction. Whether this phenomenon directly affects the uteroplacental circulation is to be assessed in future research. Full article

Background/Objectives: Inadequate cardiovascular adaptation during pregnancy impairs endothelial function and vascular resistance, contributing to complications such as pre-eclampsia (PE) and gestational hypertension (GH). Neprilysin (NEP), a protease involved in vascular regulation, has been linked to PE, but its role in endothelial function and vascular adaptation remains unclear. This pilot study investigates the associations between soluble neprilysin (sNEP) and markers of vascular and renal function in high-risk pregnancies without PE. Methods: Observed parameters were analyzed in 29 high-risk pregnant women across early, mid-, and late pregnancy. sNEP levels were analyzed alongside body mass index (BMI), endothelial dysfunction (ADMA), arterial stiffness (pulse wave velocity, PWV), retinal microvasculature (central retinal arteriolar and venular equivalents, CRAE and CRVE), and kidney function markers. The impact of gestational hypertension (GH) and prior smoking on sNEP levels was also evaluated. Results: In early and mid-pregnancy, sNEP was inversely associated with BMI. During mid-pregnancy, sNEP showed a positive correlation with CRAE and an inverse correlation with PWV, suggesting reduced arterial stiffness. By late pregnancy, sNEP was positively associated with glomerular filtration rate and inversely correlated with creatinine and protein levels, reflecting improved kidney function. Women with GH exhibited elevated sNEP, while former smokers had lower sNEP levels in early pregnancy. Conclusions: These findings suggest that sNEP plays a role in vascular and renal adaption during pregnancy, offering new perspectives on vascular tone regulation in high-risk pregnancies. Further research is needed to clarify these mechanisms and their clinical relevance. Full article

Background: Pre-eclampsia (PE) is a serious condition affecting 2–8% of pregnancies worldwide, leading to high maternal and fetal morbidity and mortality. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as potential biomarkers for various pregnancy-related pathologies, including PE. MiRNAs in plasma and serum have been extensively studied, but urinary miRNAs remain underexplored, especially during early pregnancy. This study aimed to investigate the urinary miRNA expression profiles in women with pre-eclampsia during the first and second trimesters. Materials and Methods: A prospective study was conducted using 48 urine samples from 24 pregnant women (n = 12 pre-eclampsia and n = 12 controls). Urine samples were collected in the first (9–13 weeks) and second (22–24 weeks) trimesters. MiRNA isolation, library preparation, and high-throughput sequencing were performed, followed by differential expression and enrichment analyses. Results: In the first trimester, five miRNAs were dysregulated in PE in comparison with the control group (hsa-miR-184, hsa-miR-203a-3p, hsa-miR-205-5p, hsa-miR-223-3p—downregulated; hsa-miR-1-3p—upregulated). In the second trimester, hsa-miR-205-5p and hsa-miR-223-3p were downregulated, and hsa-miR-9-5p, hsa-miR-1-3p, and hsa-miR-206 were upregulated. Conclusions: Our study identified differentially expressed miRNAs in the urine of pre-eclamptic patients during early pregnancy. These findings suggest that specific urinary miRNAs could serve as non-invasive biomarkers for the early detection and risk assessment of pre-eclampsia. The changes in the level of differential expression of miRNAs during gestation highlight their role in the progression of PE. Further research and validation with a larger cohort are needed to explore their clinical potential for improving maternal and fetal outcomes through early intervention. Full article

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). During pregnancy, physiological changes elevate cholesterol and triglyceride levels to support fetal development, which can exacerbate pre-existing conditions and lead to complications such as pre-eclampsia, gestational diabetes, and increased ASCVD risk for both mother and child. Effective management strategies are necessary, especially for pregnant women with inherited forms of dyslipidemia (i.e., familial hypertriglyceridemia, hyperchylomicronemia), where personalized dietary adjustments are crucial for successful pregnancy outcomes. Pharmacological interventions and lipoprotein apheresis may be necessary for severe cases, though their use is often limited by factors such as cost, availability, and potential fetal risks. Despite the promise of advanced therapies, their widespread application remains constrained by limited studies and high costs. Thus, a personalized, multidisciplinary approach is essential for optimizing outcomes. This review provides a comprehensive overview of current strategies and evidence-based practices for managing dyslipidemia during pregnancy, emphasizing the balance of maternal and fetal health. Additionally, it discusses the physiological changes in lipid metabolism during pregnancy and their implications, particularly for women with inherited forms of dyslipidemia. Full article

Preeclampsia is a complex pregnancy-related hypertensive disorder which poses significant risks for both maternal and fetal health. Preeclampsia affects 5–8% of pregnancies in the United States, causing a significant public health and economic burden. Despite extensive research, the etiology and pathogenesis of preeclampsia remain elusive, but have been correlated with maternal conditions such as obesity. In recent decades, the incidence of preeclampsia increased along with the prevalence of obesity among women of reproductive age. Maternal obesity has been shown to negatively affect pregnancy in almost all aspects. However, the precise mechanisms by which obesity influences preeclampsia are unclear. Ankyrin repeat and SOCS Box Containing protein 4 (ASB4) is an E3 ubiquitin ligase that can promote the degradation of a wide range of target proteins. ASB4-null mice display a full spectrum of preeclampsia-like phenotypes during pregnancy including hypertension, proteinuria, and decreased litter size. Furthermore, maternal obesity induced by a high-fat diet aggravates preeclampsia-like phenotypes in pregnant mice lacking ASB4. Variants in the ASB4 gene have been associated with obesity in humans, and a functional connection between the ASB4 gene and obesity has been established in mice. This review discusses the connections between preeclampsia, obesity, and ASB4. Full article

Background and objectives: Pre-eclampsia (PE) is a pregnancy-specific condition characterized by significant health risks for pregnant women worldwide due to its status as a multi-organ disorder. High blood pressure (hypertension) with or without proteinuria is usually considered an initial clinical sign of PE. The pathogenesis of pre-eclampsia is highly complex and likely involves multiple factors, including poorly developed uterine spiral arterioles, immunological issues, placental ischemia or infarction, and genetic abnormalities. Inflammatory cytokine production, regulated by cytokine gene polymorphisms, is one of the factors likely contributing to the development of PE. The present study aimed to assess IL-6, IL-1β, and Apo B-100 gene polymorphism and to evaluate the association of these polymorphisms with PE. Materials and Methods: This cross-sectional observational study involved 99 participants aged 16 to 45 years from Bahawal Victoria Hospital Bahawalpur, Punjab, Pakistan. The participants were divided into three groups: Group 1 (PE with severe hypertension), Group 2 (PE with hypertension), and Group 3 (control), each comprising 33 individuals. Maternal blood samples were collected, DNA was extracted, and molecular genetic analysis of the IL-6, IL-1β, and Apo B-100 genes was performed using the PCR-RFLP method. Allelic frequencies were compared, and statistical analysis was conducted using SPSS 25, applying the Hardy–Weinberg equation and chi-square test to evaluate the results. Results: There are differences in the distribution of allelic frequencies for IL-6 -174G/C (CC, GC, GG), IL-1β-511C/T (CC, CT, TT), and Apo B-100 2488 C/T (CC, CT, TT) between pre-eclamptic patients and the control group. The analysis using the Hardy–Weinberg equilibrium and chi-square test showed an association between the IL-6-174 G/C polymorphism and the severity of pre-eclampsia. Conclusions: The polymorphisms of the IL-6, IL-1β, and Apo B-100 genes revealed different alleles. The IL-6 gene alone was found to be in disequilibrium according to the Hardy–Weinberg equation, indicating a potential link to the severity of pre-eclampsia in the population studied. Full article