Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant.

Vaccinations are an essential element of public health programs around the world, which have a major impact on morbidity, mortality, and costs of the health care system. In recent years, with a better understanding of the effectiveness and safety of vaccinations, many recommendations have been developed for administering vaccines to adults. Countless physiological changes occur during pregnancy, including those affecting the immune system. Pregnant women are at increased risk of developing infections and resulting complications. According to research, vaccines are immunogenic and safe for pregnant women. Pregnancy is not an absolute contraindication to vaccination. After administration of vaccines to pregnant women, the concentration of antibodies increases, which can be transferred to the child in the second and third trimesters of pregnancy and provide protection in the first months of life. The Advisory Committee on Immunization Practices (ACIP), guidelines of the Centers for Disease Control and Prevention (CDC), and the American College of Obstetrics and Gynecology (ACOG) unanimously recommend vaccination of pregnant women if a safe vaccine is available and there is a risk of exposure of the woman to a disease that threatens herself or her developing baby. In everyday clinical practice, medical professionals should provide their patients with the necessary information on vaccinations, which may contribute to greater awareness and implementation of vaccinations. This article aims to review current global recommendations for the vaccination of pregnant and breastfeeding women, including against the Omicron variants of SARS-CoV-2.

Optimizing Delivery Strategies in Eclampsia: A Comprehensive Review on Seizure Management and Birth Methods.

Eclampsia seizure is an always serious and potentially fatal obstetric condition. Safe delivery in women with pregnancies complicated by eclampsia seizures is still one of the greatest challenges in perinatal medicine. Pregnancy should be terminated (childbirth) in the safest and least traumatic way possible. Attempting vaginal delivery can take place only exceptionally, in the event of possibly quick completion of childbirth with a stable state of the mother and the fetus. However, immediate labor via cesarean section is most often recommended. It is essential to maintain left lateral patient positioning during cesarean section. Regional anesthesia can be used only in conscious patients who are free from coagulopathy and from HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome to decrease the risk of aspiration and failed intubation attempts in preeclamptic or eclamptic women. For sudden, unexpected interventions, when a patient arrives at the hospital with an eclampsia seizure without lab results, general anesthesia can be the best option and should be performed by an experienced medical team of anesthesiologists, ready to perform difficult intubation. Magnesium sulfate is the drug that should be used first to stop eclamptic convulsions and prevent their recurrence. Intravenous antihypertensive drugs can stabilize elevated blood pressure (BP), preventing multiorgan failure and recurrent eclampsia seizure, and thus the prevention of maternal death. This article aims to review the management of seizures during pregnancy in women with eclampsia to ensure safe delivery.

Maternal Serum Angiogenic Profile and Its Correlations with Ultrasound Parameters and Perinatal Results in Normotensive and Preeclamptic Pregnancies Complicated by Fetal Growth Restriction.

FGR is a complication of pregnancy in which the fetus does not reach its programmed growth potential due to placental reasons and it is the single largest risk factor of stillbirth. Babies with FGR are at increased risk of mortality and morbidity not only in the perinatal period, but also in later life. FGR presents a huge challenge for obstetricians in terms of its detection and further monitoring of pregnancy. The ultrasound is the gold standard here; apart from assessing fetal weight, it is used to measure Doppler flows in maternal and fetal circulation. It seems that additional tests, like biochemical angiogenic factors measurement would be helpful in diagnosing FGR, identifying fetuses at risk and adjusting the surveillance model. The study aimed to assess the potential relationship between the concentration of sEng, sFlt-1, PlGF, and the sFlt-1/PlGF ratio in maternal serum at delivery and maternal and fetal Doppler flow measurements as well as perinatal outcomes in pregnancies complicated by FGR with and without PE, isolated PE cases and normal pregnancies. The use of angiogenic markers is promising not only in PE but also in FGR. Numerous correlations between ultrasound and Doppler studies, perinatal outcomes and disordered angiogenesis marker levels in maternal serum suggest that biochemical parameters have a great potential to be used as a complementary method to diagnose and monitor pregnancies with FGR. The, PlGF in particular, could play an outstanding role in this regard.

Matrix metalloproteinase-3 in preeclamptic and normotensive pregnancies complicated by foetal growth restriction.

The aim of the present study was to assess the interrelationships between the level of matrix metalloproteinase-3 in the blood serum of pregnant women and the occurrence of pregnancy complications in the form of foetal growth restriction, idiopathic or in the course of preeclampsia. Methods: A total of 245 patients were included in the study. 65 of them are normotensive patients with idiopathic foetal growth restriction (FGR group). 115 women were diagnosed with severe preeclampsia. In the group of women with preeclampsia, there were 51 patients with adequate for gestational age foetal growth and 64 patients with the foetal growth restriction in the course of severe preeclampsia. The control group consisted of 65 healthy patients with normal pregnancy course, with no cardiovascular disorders at the present and in the history, normal blood pressure and normal intrauterine foetal growth. Matrix metalloproteinase-3 (MMP-3) in maternal circulation were determined by ELISA method. Results: In our studies, we observed elevated levels of matrix metalloproteinase-3 in preeclamptic women with pregnancies complicated by FGR and significantly lower in the group of normotensive women with idiopathic FGR. The mean values of MMP-3 were 33.50 ± 65.74 ng/mL [Median (min-max) 19.19 (2.05-454.53)] in the Control group, 21.22 ± 23.28 ng/mL [Median (min-max) 16.39 (3.45-156.29)] in the FGR group, 35.96 ± 46.14 ng/mL [Median (min-max) 25.21 (4.16-253.05)] in the P group and 52.81 ± 61.61 ng/mL [Median (min-max) 32.83 (5.06-314.14)] in preeclamptic women with FGR (group PI) respectively.The assessment of MMP-3 in the serum of women with pregnancies complicated by intrauterine foetal growth restriction with normal values of blood pressure and in the group of preeclamptic patients in relation to healthy pregnant women with uncomplicated pregnancies and in relation to preeclamptic patients with normal intrauterine foetal growth is the novelty of this study. Such a strict definition of each research group seems to allow for the assessment of each pregnancy complication separately. Conclusion: It seems that higher levels of MMP-3 in preeclamptic women may suggest the need for observation towards the risk of lower birth weight of newborns. This necessitates further research and a better integration in the clinical practice.

Eclampsia: A Critical Pregnancy Complication Demanding Enhanced Maternal Care: A Review.

Eclampsia is the most serious pregnancy complication and one of the main causes of death of pregnant and delivering women. The mortality rate of young mothers is 5-20%, emphasizing the severity of this pregnancy-related disorder. Today many centers have only rare opportunities to see and deal with eclampsia cases; therefore, it is very important to bring this emergency medical condition to the attention of attending physicians. All patients with eclampsia, and after eclamptic seizures, should be treated in an intensive care unit. However, taking into account clinical realities, especially in developing countries, this is not always possible. It is necessary for all gynecologists-obstetricians to be fully prepared for eclampsia, although its occurrence is very rare. Drug treatment aims to stop eclampsia seizures and prevent reoccurrence of convulsions and complications. Magnesium sulphate is the drug of first choice used in treatment of eclampsia seizure, whereas treatment with the use of antihypertensive drugs and proper blood pressure control is one of the most important factors effectively reducing the risk of deaths or acute complications and poor pregnancy outcomes. The most urgent part of the treatment is the lifesaving procedure involving airways patency assessment, maintenance of breathing and blood circulation of the mother, securing an adequate oxygen level of the mother and thereby of the fetus, and prevention of injuries. This review aims to present an overview of the current prevalence, diagnosis, and management of eclampsia and the need for improved maternal care.

Similar Pro- and Antiangiogenic Profiles Close to Delivery in Different Clinical Presentations of Two Pregnancy Syndromes: Preeclampsia and Fetal Growth Restriction.

The purpose of this study was to evaluate serum levels of anti- and pro-angiogenic substances measured using enzyme-linked immunosorbent assays and their ratios in pregnancies complicated by different clinical subsets of placental ischemic syndrome: preeclampsia and/or fetal growth restriction. A prospective case-control study was performed consisting of 77 singleton pregnancies complicated by preeclampsia, preeclampsia with concurrent fetal growth restriction (FGR), and isolated normotensive FGR pairwise matched by gestational age with healthy pregnancies. The entire study cohort was analyzed with respect to adverse pregnancy outcomes that occurred. In all investigated subgroups, placental growth factor (PlGF) was lower and soluble endoglin (sEng), the soluble fms-like tyrosine kinase-1-sFlt-1/PlGF and sFlt-1*sEng/PlGF ratios were higher than in the control group. The differences were most strongly pronounced in the PE with concurrent FGR group and in the sFlt-1/PlGF ratio. The highest sFlt-1 values in preeclamptic patients suggest that this substance may be responsible for reaching the threshold needed for PE to develop as a maternal manifestation of ischemic placental disease. The FGR is characterized by an elevated maternal sFlt-1/PlGF ratio, which boosts at the moment of indicated delivery due to fetal risk. We concluded that angiogenic imbalance is reflective of placental disease regardless of its clinical manifestation in the mother, and may be used as support for the diagnosis and prognosis of FGR.

Lead Levels in Non-Occupationally Exposed Women with Preeclampsia.

There are many controversies regarding the relationship between lead exposure andcomplications in pregnancy. Preeclampsia (PE) is a maternal hypertensive disorder which is one of the main causes of maternal and foetal mortality. The aim of our study was to assess blood lead level (BLL) in Polish women with PE (PE group, n = 66) compared with healthy, non-pregnant women (CNP group, n = 40) and healthy pregnant women (CP group, n = 40). BLL was determined by inductively coupled plasma mass spectrometry (ICP-MS). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and BLL in the CP group were significantly lower than in the PE group (p < 0.001). Logistic regression analyses of BLL showed a significant positive relationship with the presence of PE. Furthermore, both the SBP and DBP values were positively associated with BLL. This study indicates that preeclamptic women tend to present with significantly higher BLL compared to healthy pregnant women. There were no differences in the BLL between the CP and CNP groups.

Chemical elements and preeclampsia - An overview of current problems, challenges and significance of recent research.

OBJECTIVES: Data on the elemental status, redistribution of the elements, role of occupational exposure and dietary assessment in preeclampsia (PE) are scarce. There are many disparities in the findings of essential and non-essential elements' role in PE. In this article we overview the changes in the content of selected elements in pregnancy complicated with the disorder of complex and not fully understood etiology. We have focused on important limitations and highlighted shortcomings in research from the last ten years period. METHODS: The Scopus and PubMed electronic databases have been searched for English-language articles published within the time interval 2008-2018, with full text available and with the key words "preeclampsia" and "chemical element" (i.e. separately: Cd, Pb, As, Ni, Mo, Co, Cr, Mn, Se, I, Fe, Sr, Cu, Zn, Mg, K and Na) appearing in the title, abstract or keywords. RESULTS: A total of 48 publications were eligible for this overview. Surprisingly only 4% of papers considered environmental exposure, 8%- diet and 2 %- comorbid diseases. In most published papers, occupational exposure was neglected. Meta-analysis was possible for seven elements in serum (Ca, Cu, Fe, Mg, Mn, Se, Zn), and two elements (Se, Zn) in plasma. It showed negative shift for most elements, however only several were statistically significant. CONLUSIONS: The overview of the published data on PE and chemical elements yields varied results. Some of the reasons may be the difference in not duly validated method of determination, and huge discrepancies in study designs. The lack of detailed description of studied and control population and small number of samples constitute the most common limitations of such studies. Many of them describe the use of a single analytical procedure, therefore the quality of research may be insufficient to obtain reliable results. A history of elements' status and intake before and during pregnancy is usually not examined. Dietary assessment should be done at different stages of pregnancy, and whenever possible in the periconceptional period as well. It still needs to be established whether the deficiency of certain elements or their excess may be an etiopathogenic factor and a developmental cause of PE, and if it may serve as a target of actions in the causal treatment or even prevention of the occurrence of this disease.

The Role of Nitric Oxide, ADMA, and Homocysteine in The Etiopathogenesis of Preeclampsia-Review.

Preeclampsia is a serious, pregnancy-specific, multi-organ disease process of compound aetiology. It affects 3-6% of expecting mothers worldwide and it persists as a leading cause of maternal and foetal morbidity and mortality. In fact, hallmark features of preeclampsia (PE) result from vessel involvement and demonstrate maternal endothelium as a target tissue. Growing evidence suggests that chronic placental hypoperfusion triggers the production and release of certain agents that are responsible for endothelial activation and injury. In this review, we will present the latest findings on the role of nitric oxide, asymmetric dimethylarginine (ADMA), and homocysteine in the etiopathogenesis of preeclampsia and their possible clinical implications.

The influence of nebivolol on the activity of BRL 37344 - the ß3-adrenergic receptor agonist, in the animal model of detrusor overactivity.

AIMS: The cardiotoxic effects of antimuscarinics constitute a significant restriction in their application in elderly people. Overactive bladder syndrome pharmacotherapy using compounds with cardioprotective properties would seem an ideal solution. The main goal of the study was to assess the impacts of nebivolol (NEB) on the activity of BRL 37344 - ß3-adrenergic receptor (ß3AR) agonist, in the animal model of detrusor overactivity. As both these substances can impact on the cardiovascular system, their effect on the parameters of this system and diuresis was also examined. METHODS: Retinyl acetate (RA; 0.75%) solution was used to induce detrusor overactivity in female Wistar rats. BRL and/or NEB were administered intra-arterially during cystometry in a single dose (2.5 or 5, 0.05 or 0.1 mg/kg, respectively). In addition, a 24 hours measurement of heart rate, blood pressure, and urine production was carried out. RESULTS: NEB (0.05 mg/kg) and BRL (2.5 mg/kg) monotherapy proved to have no influence on the cystometric parameters of animals with RA-induced detrusor overactivity. NEB at 0.1 mg/kg resulted in a drop in the detrusor overactivity index, similarly to BRL at 5 mg/kg. Coadministration of NEB and BRL, both at ineffective doses, decreased the detrusor overactivity index and ameliorated the nonvoiding contractions. ß3AR stimulation proved to induce tachycardia and hypertension. NEB at 0.05 mg/kg proved to ameliorate detrusor overactivity and have preventive properties against adverse cardiovascular effects of the ß3AR agonist. CONCLUSIONS: The combined application of the ß3AR agonist and NEB may improve detrusor overactivity without affecting the heart rate, blood pressure, and urine production.

Preeclampsia - Current Management and Future Approach.

Preeclampsia is one of the most serious pregnancy - specific medical conditions of increasing incidence. It remains a major cause of maternal and fetal morbidity and mortality. Although maternal mortality is especially high in developing countries, preeclampsia and its complications are one of the top four causes of maternal deaths even in developed societies. Unfortunately, yet the only effective and definitive treatment of preeclampsia is delivery of the baby and placenta, and its time depends on the disease severity and gestational age. In this review, we report principles of management of preeclampsia in the light of current international recommendations. Suggested failure of the placental development and significant role of angiogenic factors and their receptors in etiology of preeclampsia give the possibility for their future use in diagnosis and risk assessment of the disease and open new chapter of possible solutions also in the field of treatment of this serious pregnancy complication. Introduction of an advanced form of therapy that could safely prolong the duration of pregnancy would be invaluable in the area of preeclampsia management and lowering perinatal complications, especially in women with early-onset severe preeclampsia.

Angiogenic Imbalance as a Contributor of Preeclampsia.

Preeclampsia is one of the most serious pregnancy - specific medical conditions affecting 3- 6% of all gestations. It remains a leading cause of maternal and fetal morbidity and mortality. The aetiology of preeclampsia is not fully elucidated yet, although a huge progress has been made in its understanding within the last decade. Numerous studies have provided compelling evidence that an excess of some antiangiogenic molecules released by the placenta to maternal circulation, in particular soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) and decreased levels of proangiogenic substances like placental growth factor (PlGF) and vascular endothelial growth factor A (VEGF-A) play a key role in the pathogenesis of preeclampsia. In this review, we report recent knowledge about possible predictive, diagnostic and therapeutic roles of these pro- and antiangiogenic biomarkers as well as analyzed the background of their use in these fields. Discoveries in the area of circulating factors of angiogenesis are exciting and give promising perspectives for future clinical management of preeclampsia. Currently, it can be difficult, especially in developing countries due to high cost of such studies.

Altered Maternal Serum Matrix Metalloproteinases MMP-2, MMP-3, MMP-9, and MMP-13 in Severe Early- and Late-Onset Preeclampsia.

OBJECTIVE: The aim of this study was to determine whether maternal serum matrix metalloproteinases 2, 3, 9, and 13 levels differ in early- and late-onset preeclampsia and uncomplicated pregnancies. PATIENTS AND METHODS: The study was carried out in 125 pregnant women (29 with early-onset preeclampsia; 31 preeclamptic patients with late-onset preeclampsia; and 65 healthy pregnant controls). Levels of MMP-2, MMP-3, MMP-9, and MMP-13 were measured in the maternal serum using an enzyme-linked immunosorbent assay. RESULTS: Maternal serum MMP-2 levels in both the groups of preeclamptic women were significantly higher than those in the controls. Levels of MMP-3 were significantly higher in preeclamptic patients with early-onset disease; however, the MMP-3 levels in patients with late-onset preeclampsia were similar to those observed in the control subjects. MMP-9 levels were lower whereas the levels of MMP-13 were higher in both preeclamptic groups of pregnant women than in the healthy controls, but these differences were statistically insignificant. CONCLUSIONS: One important finding of the present study was that MMP-3 appears to be involved solely in early-onset preeclampsia, but not in late-onset preeclampsia. Higher levels of MMP-2 and MMP-13 and lower levels of MMP-9 seem to be related to both early- and late-onset severe preeclampsia.

The relation of maternal serum eNOS, NOSTRIN and ADMA levels with aetiopathogenesis of preeclampsia and/or intrauterine fetal growth restriction.

OBJECTIVE: The aim of present study was to assess the maternal serum endothelial nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric dimethylarginine (ADMA) levels in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants. PATIENTS AND METHODS: The study was performed on 65 normotensive pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51 preeclamptic women with normal intrauterine fetal growth and 65 healthy normotensive pregnant women with singleton uncomplicated pregnancies. Severe preeclampsia was defined as blood pressure> 160/110 mmHg with proteinuria> 5 g in a 24-h urinary protein excretion. IUGR were classified when the weight of the fetus was below the 10th centiles with disturbed placental function and abnormal ultrasonographic examination. The diagnosis was confirmed by the infant's weight at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were determined using a sandwich enzyme-linked immunosorbent assays. RESULTS: There were no statistically significant differences in the eNOS and NOSTRIN levels between studied groups of women. Increased levels of ADMA in both preeclamptic groups and in women with pregnancies complicated by isolated IUGR were observed. CONCLUSIONS: Our results allow the conclusion that impaired NO bioavailability in pregnancies complicated by severe preeclampsia and/or IUGR result not from a reduced level or activity of eNOS or from its disturbed intracellular transport, but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.

Changes in Heligmosomoides polygyrus glycoprotein pattern by saponins impact the BALB/c mice immune response.

Saponins of marigold (Calendula officinalis), in particular derivatives of 3-O-monoglucuronide of oleanolic acid, are able to reduce infectivity of Heligmosomoides polygyrus in mice. The purpose of this study was to understand the immune activation provoked by third-stage larvae exposed to marigold glucuronides. We also examined the pattern of glycosylation of larval antigens which appeared to be crucial for induction of cytokine production in BALB/c mice; higher concentrations of IL-6, IFN-γ, IL-10 and TNF-α were observed in serum or intestine one week post infection. Three weeks later, in the chronic phase of infection, cells in culture were able to produce IL-6, IFN-γ, TNF-α and IL-17. Restimulation of cells with H. polygyrus antigen resulted in reduced production of IL-6, and TNF-α. The pattern of cytokine production co-existed with reduced expression of terminal glucose, α-linked mannose, N-acetyl-galactosamine, ß-galactose, N-acetyl-glucosamine and α-fucose in several protein bands. Galactose, as a new terminal carbohydrate residue appeared in 20-24kDa protein bands. The number of immunogenic epitopes in parasitic antigens was reduced; only three protein bands of 56, 26 and 12kDa were recognized by IgG1. These studies provide a model system to find the glycosylated molecules expressed on nematodes that improve establishment and survival and characterize cytokine production in mice infected with larvae exposed to saponin. Identification of these molecules is the first step in the recognition of key antigenic epitopes able to induce protective or tolerogenic immune responses.

A comparison of maternal serum levels of endothelial nitric oxide synthase, asymmetric dimethylarginine, and homocysteine in normal and preeclamptic pregnancies.

BACKGROUND: The aim of this study was to determine the maternal serum concentrations of eNOS, ADMA, and homocysteine in preeclamptic pregnancies. MATERIAL AND 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.

Elevated maternal serum sP-selectin levels in preeclamptic pregnancies with and without intrauterine fetal growth restriction, but not in normotensive pregnancies complicated by isolated IUGR.

BACKGROUND: The aim of this study was to show differences of maternal serum sP-selectin levels in pregnancies complicated by intrauterine fetal growth restriction (IUGR) in the course of preeclampsia and to compare the results with normotensive pregnant women with isolated IUGR. These studies were also conducted on preeclamptic pregnancies with appropriate-for-gestational-age weight infants and on the control normotensive pregnant women. MATERIAL AND METHODS: The study was carried out on 55 patients with pregnancy complicated by fetal growth restriction in the course of preeclampsia, 70 normotensive patients with pregnancies complicated by isolated IUGR, 39 preeclamptic patients with appropriate-for-gestational-age weight fetuses and 54 healthy normotensive pregnant patients with normal fetal growth. Maternal serum levels of sP-selectin were determined using the enzyme-linked immunosorbent assay. RESULTS: Levels of sP-selectin were higher in women with pregnancy complicated by preeclampsia with and without IUGR; whereas, in the group of normotensive pregnant women with isolated fetal growth restriction, serum sP-selectin levels tended to be lower than in the control subjects, but this difference was not statistically significant. The mean values were 192.05±70.96 ng/mL in the IUGR group, 293.18±222.92 ng/mL in the PI group, 379.78±353.13 ng/mL in the P group and 227.96±134.04 ng/mL in the healthy controls (p<0.001*). CONCLUSIONS: Our findings may suggest that the elevated level of the soluble P-selectin is associated with preeclampsia, and that it may confirm the presence of platelet and endothelial activation, the presence of the hypercoagulant state and may be due to the systemic inflammatory response in this serious pregnancy disorder.

Differences in the association between maternal serum homocysteine and ADMA levels in women with pregnancies complicated by preeclampsia and/or intrauterine growth restriction.

OBJECTIVE: The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction. METHODS: The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays. RESULTS: A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia. CONCLUSION: These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.