The Effects of Vitamin D Supplementation before 20 Weeks of Gestation on Preeclampsia: A Systematic Review.

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide. The role of vitamin D supplementation during early pregnancy in the prevention of preeclampsia remains unclear. Our objective was to synthesize and critically appraise the available evidence from observational and interventional studies to determine the effects of early pregnancy vitamin D supplementation on the risk of preeclampsia. A systematic review was conducted in March 2023 using PubMed, Web of Science, Cochrane, and Scopus databases, including literature published up to February 2023. In adherence to PRISMA guidelines, a structured and systematic search strategy was employed. A total of five studies were included in the review, encompassing 1474 patients. Overall, vitamin D supplementation during early pregnancy was associated with a reduced incidence of preeclampsia in all studies (ORs ranging from 0.26 to 0.31), while others showed an increased risk of preeclampsia with low vitamin D levels during the first trimester (ORs of 4.60, 1.94, and 2.52). However, other studies found no significant protective effect but good overall safety for various vitamin D dosages administered during the first trimester. Nevertheless, variations in vitamin D dosage, the timing of supplementation, and definitions of vitamin D insufficiency may have contributed to the inconsistencies in the observed outcomes. Some studies reported significant secondary outcomes, such as a reduction in blood pressure, preterm labor, and improved neonatal outcomes, such as birth weight. The evidence from this systematic review suggests that early pregnancy vitamin D supplementation may have a role in reducing the risk of preeclampsia. However, inconsistencies in the timing of supplementation, dosages, and methodological differences between studies highlight the need for further research to determine the optimal supplementation strategy and to clarify the relationship between vitamin D and preeclampsia risk.

A Prospective Analysis of Vitamin D Levels in Pregnant Women Diagnosed with Gestational Hypertension after SARS-CoV-2 Infection.

The great majority of existing studies suggests that the prognosis and outcomes of SARS-CoV-2 infections are improved with adequate vitamin D levels, with or without supplementation. Simultaneously, whether vitamin D supplementation during pregnancy lessens the chance of developing gestational hypertension is controversial. The objective of the present research was to evaluate whether vitamin D levels during pregnancy differ substantially among pregnant women who develop gestational hypertension following SARS-CoV-2 infection. The current research was designed as a prospective cohort following the pregnant women admitted to our clinic with COVID-19 until 36 weeks of gestation. Total vitamin D (25(OH)D) levels were measured in the three study groups in which pregnant women with COVID-19 during pregnancy and a diagnosis of hypertension after 20 weeks of gestation were considered the group of cases (GH-CoV). The second group (CoV) included those with COVID-19 and no hypertension, while the third group (GH) included those with hypertension and no COVID-19. It was observed that 64.4% of SARS-CoV-2 infections in the group of cases occurred during the first trimester, compared to 29.2% in the first trimester among the controls who did not develop GH. Normal vitamin D levels were measured at admission in a significantly higher proportion of pregnant women without GH (68.8% in the CoV group vs. 47.9% in the GH-CoV group and 45.8% in the GH group). At 36 weeks of gestation, the median values of 25(OH)D in the CoV group was 34.4 (26.9-39.7) ng/mL compared to 27.9 (16.2-32.4) ng/mL in the GH-CoV group and 29.5 ng/mL (18.4-33.2) in the GH group, while the blood pressure measurements remained over 140 mmHg among the groups who developed GH. There was a statistically significant negative association between serum 25(OH)D levels and systolic blood pressure (rho = -0.295; p-value = 0.031); however, the risk of developing GH was not significantly higher among pregnant women with COVID-19 if the vitamin D levels were insufficient (OR = 1.19; p-value = 0.092) or deficient (OR = 1.26; p-value = 0.057). Although insufficient or deficient vitamin D among pregnant women with COVID-19 was not an independent risk factor for the development of GH, it is likely that an association between first-trimester SARS-CoV-2 infection and low vitamin D plays a key role in developing gestational hypertension.

A Cross-Sectional Analysis of Intimacy Problems, Stress Levels, and Couple Satisfaction among Women with Thrombophilia Affected by Recurrent Pregnancy Loss.

Recurrent pregnancy loss (RPL) is one of the most challenging and difficult areas of reproductive treatment due to the immense emotional suffering inflicted on families and couples affected by RPL. As a result, it is predicted that couples experiencing recurrent pregnancy loss would have an increase in marital problems, stress levels, and anxiety, preventing them from achieving their family goals. The current cross-sectional study aimed to target pregnant women with thrombophilia with a history of RPL to observe their intimacy problems, stress levels, and couple satisfaction by completing a series of digital questionnaires. These patients were considered as the reference group, while the control group was formed by other women with thrombophilia and a history of RPL who eventually achieved pregnancy and gave birth. A total of 238 complete questionnaires were recorded (157 in the reference group and 81 in the control group). It was observed that women in the reference group who did not give birth had a significantly higher proportion of three or more pregnancy attempts (54.1% vs. 39.5%) and a significantly higher proportion of three more pregnancy losses (68.8% vs. 55.6%). It was observed that patients in the reference group were more likely to be emotion-oriented (42.7% vs. 27.2%). Also, women in the reference group had higher levels of dissatisfaction and lower levels of self-acceptance, pleasure, and marital quality scores. The total SII and DSCS scores were significantly lower than women with thrombophilia with a history of RPL who eventually gave birth. Women from the reference group had significantly greater intimacy problems and stress levels while having lower openness scores and self-esteem scores than women in the control group. It is possible that women with thrombophilia and recurrent pregnancy loss are more dissatisfied with their marriages than those who subsequently had one child. Since the financial status of those who achieved pregnancy was observed to be higher, it is likely that they achieved pregnancy by ART interventions, as they reported in questionnaires. It is important to target families afflicted by thrombophilia and other reasons for infertility to ease their access to ART therapies. By achieving their objectives, affected families will minimize dissatisfaction, divorce rates, and stress.

A Comparative Analysis of NT-proBNP Levels in Pregnant Women and the Impact of SARS-CoV-2 Infection: Influence on Birth Outcome.

BACKGROUND: The cardiac biomarker NT-proBNP is released by the ventricles in response to increased cardiac wall tension, showing cardiac activity in heart failure. The primary objective of this comparative study was to analyze the variations of NT-proBNP levels among pregnant patients and to determine the potential influence of SARS-CoV-2 infection on these values. Secondly, the study focused on NT-proBNP levels and their influence on the type of birth. METHODS: Blood samples were taken from 160 pregnant mothers in order to determine, through the solid-phase enzyme-linked immunosorbent assay (ELISA) method, the NT-proBNP concentrations from the plasma. The cohort was separated into two distinct groups based on SARS-CoV-2 diagnostic results: negative to the infection, and positive to the infection. RESULTS: The SARS-CoV-2-positive group of patients presented with higher levels of NT-proBNP and had higher rates of cesarean sections. (4) Conclusions: Our research highlights the crucial relationship between elevated NT-proBNP values and the mode of giving birth, natural delivery or cesarean section, and also the influence of SARS-CoV-2 viral infection and this biomarker.

A Retrospective Assessment of Thrombophilia in Pregnant Women with First and Second Trimester Pregnancy Loss.

Recurrent Pregnancy Loss (RPL) affects between 1% to 5% of women of reproductive age. It is widely believed that RPL is a complex disorder that is influenced by chromosomal abnormalities, genetic mutations, uterine anatomic deformity, endocrine dysfunction, immunologic factors, infections, and the environment. Thrombotic disorders are a frequent cause of RPL, accounting for almost half of all cases; however, in the rest of the cases, the cause of RPL remains unclear. Therefore, in this study, it was planned to determine the genetic mutations involved in RPL during the first and second trimester of pregnancy. An observational retrospective cohort study was conducted in 2021, collecting data from 157 first trimester miscarriages and 54 s trimester pregnancies. All patients with a panel of laboratory and genetic analysis for thrombophilia were included for data analysis. It was observed that four factors were significantly more prevalent in one of the groups. Factor V Leiden (FVL) homozygosity and antiphospholipid syndrome (APS) antibodies were statistically significantly more common in pregnant women who suffered first trimester pregnancy losses. On the other hand, Protein C deficiency and Glycoprotein Ia polymorphism were statistically significantly more frequent in the second trimester group. The strongest independent risk factors for first trimester pregnancy loss were FVL and prothrombin (PT) compound mutations (OR = 3.11), followed by FVL homozygous mutation (OR = 3.66), and APS antibodies (OR = 4.47). Regarding second trimester pregnancy loss risk factors, the strongest were FVL and PT compound (OR = 3.24), followed by Glycoprotein Ia polymorphism (OR = 3.61), and respectively, APS antibodies (OR = 3.85). Numerous thrombophilic risk factors for early and late pregnancy loss have been found, including several mutations that seem to occur more often either during the first or the second trimester. Even though we are aware of risk-free and efficient diagnostics for thrombophilia abnormalities, no intervention has been proved to be clearly successful after the detection of these variables.

The Influence of Maternal Vitamin D Supplementation in Pregnancies Associated with Preeclampsia: A Case-Control Study.

Preeclampsia is a pregnancy-specific illness that is hypothesized to occur due to vitamin D deficiency during pregnancy. Therefore, vitamin D supplementation in early pregnancy should be explored for preventing preeclampsia and promoting neonatal well-being. The present study follows a case-control analysis that aims to determine the effect of vitamin D supplements on reducing the probability of recurrent preeclampsia. We identified 59 patients for the control group without vitamin D supplementation during pregnancy, while 139 patients were included in the cases group of pregnant women with a history of preeclampsia who confirmed taking daily vitamin D supplements in either 2000 UI or 4000 UI until the 36th week of pregnancy. There were 61 (80.3%) patients with a normal serum vitamin D level measured at 32 weeks in the pregnant women who took a daily dose of 4000 UI vitamin D and 43 (68.3%) in those who took a 2000 UI dose of vitamin D, compared to just 32 (54.2%) in those who did not take vitamin D at all. Regarding the blood pressure of pregnant women measured at 32 weeks, it was observed that 20.3% were hypertensive in the no supplementation group, compared to only 11.1% and 6.6% in those who were taking vitamin D during pregnancy (p-value = 0.049). Serum vitamin D levels at 32 weeks were measured at an average value of 23.9 ng/mL, compared with 28.4 ng/mL in the group taking a 2000 UI daily dose and 33.6 in those who supplemented with 4000 UI daily (p-value < 0.001). Proteinuria was identified more often in the group at risk for preeclampsia who did not take vitamin D supplements, while systolic blood pressure (p-value = 0.036) as well as diastolic blood pressure (p-value = 0.012), were all identified to have significantly higher values in the pregnant women with a history of preeclampsia that did not take vitamin D during the current pregnancy. The significant risk factors for preeclampsia development in pregnant patients at risk are: insufficient vitamin D serum levels (<20 ng/mL), OR = 2.52; no vitamin D supplementation, OR = 1.46; more than two pregnancies, OR = 1.89; gestational diabetes mellitus, OR = 1.66; and cardiovascular comorbidities, OR = 2.18. These findings imply that vitamin D has a role in the preservation of placental function and, therefore, in the prevention of the development of late preeclampsia. Pregnant mothers who supplemented their diets with vitamin D were protected against preeclampsia recurrence. Vitamin D supplementation during pregnancy may aid in the prevention of gestational hypertension and preeclampsia.

The Impact of SARS-CoV-2 Pandemic on Patients Undergoing Radiation Therapy for Advanced Cervical Cancer at a Romanian Academic Center: A Four-Year Retrospective Analysis.

Background and Objectives: Throughout the COVID-19 pandemic, health systems worldwide adapted to support COVID-19 patients while continuing to provide assistance to patients with other potentially fatal illnesses. While patients with cancer may be at an elevated risk of severe COVID-19-related complications, their oncologic therapies generally cannot be postponed indefinitely without a negative effect on outcomes. Taking this into account, a thorough examination of the therapy management of various cancers is necessary, such as cervical cancer. Therefore, we aimed to develop a retrospective cohort study to measure the impact of the COVID-19 pandemic on the delivery of cancer care services for women diagnosed with cervical cancer staged IB2-IVA, necessitating chemo- and radiotherapy in Romania, as well as determine the difference in cervical cancer staging between the pandemic and pre-pandemic period. Materials and Methods: Using a multicentric hospital database, we designed a retrospective study to compare the last 24 months of the pre-pandemic period to the first 24 months of the SARS-CoV-2 pandemic to evaluate the variation in the proportion of women diagnosed with cervical cancer and the percentage of inoperable cases requiring chemotherapy and radiotherapy, as well as to detail their clinical presentation and other findings. Results: We observed that the likelihood of cervical cancer patients requiring radiation therapy at a later stage than before the pandemic increased by about 20% during the COVID-19 pandemic. Patients at an advanced FIGO stage of cervical cancer had a 3.39 higher likelihood of disease progression after radiotherapy (CI [2.06−4.21], p-value < 0.001), followed by tumor size at diagnosis with a hazard ratio (HR) of 3.12 (CI [2.24−4.00], p-value < 0.001). The factors related to the COVID-19 pandemic, postponed treatment and missed appointments, were also identified as significant risk factors for cervical cancer progression (HR = 2.51 and HR = 2.24, respectively). Conclusions We predict that there will be a considerable rise in cervical cancer cases over the next several years based on existing data and that expanding screening and treatment capacity will attenuate this with a minimal increase in morbidity and fatality.

The Influence of Maternal Factors on Neonatal Intensive Care Unit Admission and In-Hospital Mortality in Premature Newborns from Western Romania: A Population-Based Study.

Background and Objectives: Neonatal mortality is a global public health issue, disproportionately affecting low- and middle-income nations. Although Romania is a high-income nation, according to the European Union's most recent demographic data, it had the second-highest infant death rate in 2019. Although significant progress has been made in the last three decades in lowering newborn mortality, more initiatives to accelerate progress are required to meet the 2030 Sustainable Development Goals (SDG) objective. Therefore, we aimed to develop an observational study to determine the influence of maternal factors on in-hospital neonatal intensive care unit admission and mortality in premature infants born in western Romania. While newborn mortality has decreased globally, the pace of decline is far less than what is desired. Materials and Methods: A retrospective study comprising 328 premature patients and 422 full-term newborns, was developed at a tertiary obstetrics and gynecology clinic in western Romania, comprising the period of the last 24 months before the COVID-19 pandemic and the first 24 months of the pandemic. Results: The following variables were identified as statistically significant risk factors for neonatal intensive care unit admission: age > 35 years, OR = 1.59; twin births, OR = 1.14; low gestational age, OR = 1.66; preeclampsia, OR = 2.33; and peripartum infection, OR = 2.25. The same risk factors, with the exception of twin births, were significantly associated with in-hospital neonatal mortality. Except for a longer duration of maternal hospitalization and neonatal therapy with surfactant, steroids, and antibiotics, the COVID-19 pandemic did not cause significant differences in the evolution and outcomes of preterm newborns. Conclusions: The major maternal risk factors for NICU admission were advanced age, twin pregnancy, low gestational age, preeclampsia, and peripartum infection. Additionally, these characteristics contributed to a high likelihood of death, despite adequate access to medical care and advanced life support for the neonates. Understanding the causes of morbidity and death in neonates admitted to the neonatal intensive care unit enables better prioritization and planning of health services, resource reallocation, and care quality improvement.

Challenges in Diagnosis and Prevention of Iatrogenic Endometriosis as a Long-Term Surgical Complication after C-Section.

Endometriosis is a gynecological condition caused by the development of endometrial tissue outside the uterine cavity. Naturally, it commonly occurs at locations such as the ovaries and pelvic peritoneum. However, ectopic endometrial tissue may be discovered outside of the typical sites, suggesting the possibility of iatrogenic seeding after gynecological operations. Based on this hypothesis, we developed a study aiming to establish the root cause of atypical implantation of endometrial foci, as the main end point, and to determine diagnostic features and risk factors for this condition, as a secondary target. The research followed a retrospective design, including a total of 126 patients with endometriosis who met the inclusion criteria. A group of 71 patients with a history of c-section was compared with a control group of patients with endometriosis and no history of c-section. Endometriosis that developed inside or in close proximity to surgical incisions of asymptomatic patients before surgical intervention was defined as iatrogenic endometriosis. Compared with patients who did not have a c-section, the c-section group had significantly more minimally invasive pelvic procedures and multiple adhesions and endometriosis foci at intraoperative look (52.1% vs. 34.5%, respectively 52.1% vs. 29.1%). The most common location for endometriosis lesions in patients with prior c-section was the abdominal wall (42.2% vs. 5.4%), although the size of foci was significantly smaller by size and weight (32.2 mm vs. 34.8 mm, respectively 48.6 g vs. 53.1 g). The abdominal wall endometriosis was significantly associated with minimally invasive pelvic procedures (correlation coefficient = 0.469, p-value = 0.001) and c-section (correlation coefficient = 0.523, p-value = 0.001). A multivariate regression analysis identified prior c-section as an independent risk factor for abdominal wall endometriosis (OR = 1.85, p-value < 0.001). We advocate for strict protocols to be implemented and followed during c-section and minimally invasive procedures involving the pelvic region to ensure minimum spillage of endometrial cells. Further research should be developed to determine the method of abdominal and surgical site irrigation that can significantly reduce the risk of implantation of viable endometrial cells. Understanding all details of iatrogenic endometriosis will lead to the development of non-invasive disease diagnosis and minimally invasive procedures that have the potential to reduce postoperative complications.

The Influence of Nutritional Supplementation for Iron Deficiency Anemia on Pregnancies Associated with SARS-CoV-2 Infection.

Anemia is a very common occurrence during pregnancy, with important variations during each trimester. Anemia was also considered as a risk factor for severity and negative outcomes in patients with SARS-CoV-2 infection. As the COVID-19 pandemic poses a significant threat for pregnant women in terms of infection risk and access to care, we developed a study to determine the impact of nutritional supplementation for iron deficiency anemia in correlation with the status of SARS-CoV-2 infection. In a case-control design, we identified 446 pregnancies that matched our inclusion criteria from the hospital database. The cases and controls were stratified by SARS-CoV-2 infection history to observe the association between exposure and outcomes in both the mother and the newborn. A total of 95 pregnant women were diagnosed with COVID-19, having a significantly higher proportion of iron deficiency anemia. Low birth weight, prematurity, and lower APGAR scores were statistically more often occurring in the COVID-19 group. Birth weight showed a wide variation by nutritional supplementation during pregnancy. A daily combination of iron and folate was the optimal choice to normalize the weight at birth. The complete blood count and laboratory studies for iron deficiency showed significantly decreased levels in association with SARS-CoV-2 exposure. Puerperal infection, emergency c-section, and small for gestational age were strongly associated with anemia in patients with COVID-19. It is imperative to screen for iron and folate deficiency in pregnancies at risk for complications, and it is recommended to supplement the nutritional intake of these two to promote the normal development and growth of the newborn and avoid multiple complications during pregnancy in the COVID-19 pandemic setting.

Heavy metal ion concentration in the amniotic fluid of preterm and term pregnancies from two cities with different industrial output.

The growth and development of the fetus is a complex phenomenon that can be influenced by several variables. High quantities of heavy metal ions in the amniotic fluid have been linked to poor health, especially in industrial, polluted and poor areas. The aim of the present study was to assess the differences in the concentration of these ions between preterm (weeks 15-37) and term pregnancies (starting at week 37). Another objective was to compare pregnancies from two cities with different industry levels. Two sample lots from two Romanian cities were analyzed. A total of 100 patients from Timisoara were compared with 60 from Petrosani, a heavy industry city in Romania. Demographic data were collected, and amniocentesis was performed on all women. Lead (Pb), copper (Cu), nickel (Ni), cadmium (Cd), arsenic (As), iron (Fe) and zinc (Zn) concentrations were assessed. Descriptive and analytical statistics were performed using the Mann-Whitney U test for non-parametric data and the Fisher's exact test for categorical data. In addition, categorical data was represented graphically. In the Timisoara cohort, the differences in heavy metal concentrations between preterm and term pregnancies were not statistically significant. In the Petrosani cohort, however, the concentrations of Zn (P=0.02606) and Cd (P=0.01512) were higher in preterm than in term pregnancies. When comparing the two cohorts as a whole, the concentration of Pb (P=0.04513), Cd (P=0.00002), As (P=0.03027) and Zn (P<0.00001) were higher in the patients from Petrosani than in those from Timisoara. Only Cu concentrations were higher in the Timisoara cohort (P<0.00001). The concentrations of Ni (P=0.78150) and Fe (P=0.44540) did not differ statistically. Thus, amniocentesis is an important diagnostic and exploratory tool in determining differences in the concentrations of elements such as heavy metal ions. Research over a longer period of time should be carried out to examine the relation between heavy metal ions concentration and possible postnatal health outcomes.

Simultaneous Seroprevalence to Toxoplasma gondii, Cytomegalovirus and Rubella Virus in Childbearing Women from Western Romania.

Background and Objectives: Toxoplasma gondii, cytomegalovirus (CMV) and rubella virus, besides other agents, belong to a group named the TORCH complex. Research on the epidemiology of these agents in women is of particular interest, as primary infection during pregnancy could cause severe damage to the fetus. Women who had contracted infection before pregnancy develop IgG antibodies, so the fetus is protected in case of contact with the same agent. Our scope was to identify the childbearing women simultaneously protected or susceptible to a primary infection to two or three agents mentioned above. Materials and Methods: A cross-sectional study was performed on 6961 fertile Caucasian women from Western Romania, to analyze the simultaneous seroprevalence to two or three of the pathogens from the TORCH complex: Toxoplasma gondii, CMV, and rubella virus. Sampling was conducted at two time points: 2008-2010 (group 1; 1461 participants) and 2015-2018 (group 2; 5500 participants). Results: The percentage of women simultaneously seropositive to IgG-anti-Toxoplasma gondii/IgG-anti-CMV, IgG-anti-Toxoplasma gondii/IgG-anti-rubella, IgG-anti-CMV/IgG-anti-rubella or IgG-anti-Toxoplasma gondii and IgG-anti-CMV/IgG-anti-rubella antibodies decreased between the two groups (2008-2010 vs. 2015-2018): 41.4% vs. 36.1%, OR = 0.79, p = 0.0002; 41.8% vs. 35.7%, OR = 0.77, p < 0.0001; 88.9% vs. 83.6%, OR = 0.63, p < 0.0001; 39.6% vs. 33.2%, OR = 0.75, p < 0.0001. When comparing women from urban and rural areas, the simultaneous seroprevalence was higher in rural areas. In women tested 2008-2010 (group 1) the simultaneous seroprevalence (urban vs. rural) was: 38.4% vs. 49.1%, OR = 1.54, p = 0.0002; 38.4% vs. 50.6%, OR = 1.64, p < 0.0001; 88.8% vs. 89.2%, OR = 1.04, NS; 36.4% vs. 47.7%, OR = 1.58, p = 0.0001. A similar trend was found in women tested in group 2. Conclusions: The rate of simultaneous seropositivity to Toxoplasma gondii, CMV and rubella virus among Romanian women of reproductive age decreased significantly between 2008-2010 and 2015-2018 and the susceptibility to infections increased. It is necessary to apply increased prevention measures among susceptible pregnant women.