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.

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.

The Impact of Latent Cytomegalovirus Infection on Spontaneous Abortion History and Pregnancy Outcomes in Romanian Pregnant Women.

Cytomegalovirus (CMV), a DNA virus that belongs to the Orthoherpesviridae family, infects 40-100% of people. Primary/non-primary CMV infection during pregnancy could cause fetal disabilities. After primary infection, CMV causes a latent infection and resides in cells of the myeloid compartment (CD34+, monocytes). Few studies have analyzed the impact of latent CMV infections on miscarriage history, pregnancy complications, and neonatal outcomes. METHODS: Serum samples from 806 pregnant women (28.29 ± 4.50 years old) who came for a consultation at the Timisoara Clinical Emergency City Hospital between 2008 and 2010 were tested for anti-CMV IgM/IgG antibodies, and data about demography, obstetrical history, pregnancy complications, birth, and neonate were collected. The data were compared between the groups with and without latent CMV infection, and statistical significance was calculated. RESULTS: We did not find a difference regarding cesarean section (OR = 0.916, p = 0.856), placental abruption (OR = 1.004, p = 1.00), pregnancy-induced hypertension rate (OR = 1.078, p = 1.00), secondary sex ratio (0.882, p = 0.857), APGAR score (p = 0.225), gestational age at birth (p = 0.434), or birth weight (p = 0.365). A borderline significant difference was found regarding the presence of miscarriage history: OR = 8.467, p = 0.051. CONCLUSIONS: The presence of latent CMV infection does not affect the likelihood of complications in healthy women. A borderline significantly higher prevalence of miscarriage history was found in women with latent CMV infection.

Prevalence of Gestational Diabetes in preCOVID-19 and COVID-19 Years and Its Impact on Pregnancy: A 5-Year Retrospective Study.

Gestational diabetes mellitus (GDM) affects a total of 3% to 9% of all pregnancies. It has a high impact on both mother and baby, increases the perinatal risks, and predicts the presence of long-term chronic metabolic complications. The aim of our study is to determine the incidence of GDM in tertiary hospitals in the west part of Romania to lay out the risk factors associated with GDM and to observe the evolution of pregnancy among patients with this pathology by emphasizing the state of birth of the fetus, the birth weight, and the way of birth. We also want to compare the prevalence of GDM in preCOVID-19 (Coronavirus disease) versus COVID-19 years. The study took place between January 2017 and December 2021 at the Municipal Emergency Hospital of Timisoara, Romania. The proportion of births with GDM was significantly increased during the COVID-19 period compared to the preCOVID-19 period (chi2 Fisher exact test, p < 0.001). The period 2020−2021 represents a significant risk factor for GDM births (OR = 1.87, with 95% CI = [1.30, 2.67]). COVID years represent a risk period for developing gestational diabetes, which can be explained by reduced physical activity, anxiety, or modified dietary habits, even if the follow-up period was not impacted.

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.

COVID-19 Pandemic Effects on Cervical Cancer Diagnosis and Management: A Population-Based Study in Romania.

The Pap test plays a significant role worldwide in the early diagnosis of and high curability rates for cervical cancer. However, the coronavirus disease 2019 (COVID-19) pandemic necessitated the use of multiple drastic measures to stop the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, limiting women's access to essential invasive and non-invasive investigations for cervical cancer diagnosis. Therefore, we aimed to determine the impact the COVID-19 pandemic had on cancer diagnosis and management in western Romania. A retrospective study design allowed us to compare the last 24 months of the pre-pandemic period with the first 24 months of the COVID-19 pandemic to determine the change in volume of cervical screening tests, the number of newly diagnosed cases and their severity, and the access to cancer care. A drastic 75.5% decrease in the volume of tests was observed in April 2020 during the first lockdown, after which the volume of cases decreased by up to 36.1% in December 2021. The total volume loss of tests during the first 24 months of the pandemic was 49.9%. The percentage of late-stage cervical cancers (III-IV) rose by 17%, while the number of newly diagnosed cancers in our outpatient clinic was significantly lower than the baseline, with a 45% drop. The access to cancer care was negatively influenced, with 9.2% more patients waiting longer to receive test results over four weeks, while taking longer to seek cancer care after diagnosis (6.4 months vs. 4.1 months pre-pandemic) and missing significantly more appointments. The COVID-19 pandemic had a significantly negative impact on cervical cancer diagnosis and management during the first 24 months compared with the same period before the pandemic. Although the numbers are now recovering, there is still a big gap, meaning that many cervical cancer cases were potentially missed. We recommend further interventions to reduce the gap between the pre-pandemic and pandemic period.

COVID-19 Pandemic Impact on Surgical Treatment Methods for Early-Stage Cervical Cancer: A Population-Based Study in Romania.

Being one of the most common malignancies in young women, cervical cancer is frequently successfully screened around the world. Early detection enables for an important number of curative options that allow for more than 90% of patients to survive more than three years without cancer relapse. Unfortunately, the COVID-19 pandemic put tremendous pressure on healthcare systems and access to cancer care, determining us to develop a study on the influence the pandemic had on surgical care of cervical cancer, and to assess changes in its management and outcomes. A retrospective study design allowed us to compare cervical cancer trends of the last 48 months of the pre-pandemic period with the first 24 months during the COVID-19 pandemic, using the database from the Timis County Emergency Clinical Hospital. New cases of cervical cancer presented to our clinic in more advanced stages (34.6% cases of FIGO stage III during the pandemic vs. 22.4% before the pandemic, p-value = 0.047). These patients faced significantly more changes in treatment plans, postponed surgeries, and postponed radio-chemotherapy treatment. From the full cohort of cervical cancer patients, 160 were early stages eligible for curative intervention who completed a three-year follow-up period. The disease-free survival and overall survival were not influenced by the surgical treatment of choice, or by the SARS-CoV-2 infection (log-rank p-value = 0.449, respectively log-rank p-value = 0.608). The individual risk factors identified for the three-year mortality risk were independent of the SARS-CoV-2 infection and treatment changes during the COVID-19 pandemic. We observed significantly fewer cases of cervical cancer diagnosed per year during the first 24 months of the COVID-19 pandemic, blaming the changes in healthcare system regulations that failed to offer the same conditions as before the pandemic. Even though we did not observe significant changes in disease-free survival of early-stage cervical cancers, we expect the excess of cases diagnosed in later stages to have lower survival rates, imposing the healthcare systems to consider different strategies for these patients while the pandemic is still ongoing.

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 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.

The Impact of Latent Toxoplasma gondii Infection on Spontaneous Abortion History and Pregnancy Outcomes: A Large-Scale Study.

BACKGROUND: Toxoplasma gondii (TG), a zoonotic protozoan parasite, belongs to a group of TORCH infectious agents, which can cause severe damage to the fetus if a primary infection occurs during pregnancy. After primary infection, TG rests lifelong in human organisms causing a latent infection. Most studies have analyzed the consequences of acute, but not latent, TG infection. This study analyzed the impact of latent toxoplasmosis on spontaneous abortion history, pregnancy complication rate and neonatal outcome. METHODS: IgG and IgM anti-TG antibodies were tested in 806 pregnant women who were consulted at the Timisoara Clinical Emergency Hospital between 2008 and 2010. Demographic data, obstetrical history, and data about the pregnancy complications, birth and neonate were collected for each woman and comparisons between the groups, with and without latent TG infection, were made. RESULTS: This study did not show differences between groups regarding the history of spontaneous abortion (OR = 1.288, p = 0.333), cesarean section (OR = 1.021, p = 0.884), placental abruption (OR 0.995, p = 0.266), pregnancy-induced hypertension rate (OR 1.083, p = 0.846), secondary sex ratio (1.043, p = 0.776), 1' APGAR score at birth (p = 0.544), gestational age at birth (p = 0.491) or birth weight (p = 0.257). CONCLUSIONS: The observed differences between the rate of pregnancy complications in the two groups of pregnant women with and without latent infection with TG, did not reach a statistical significance.

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.