Gestational Weight Gain, Pregnancy Related Complications and the Short-Term Risks for the Offspring.

BACKGROUND AND OBJECTIVES: Maternal obesity influences pregnancy course in several different manners, and imbalanced nutrition during pregnancy may lead to various adverse pregnancy outcomes. Additionally, nutritional status during pregnancy may have implications for the health of the offspring and may possibly influence early motor development in children. The aim of this study was to assess the impact of excessive gestational weight gain (EGWG) on pregnancy outcomes and infant's motor development within the first twelve months of life. MATERIALS AND METHODS: The study included 200 participants divided in two groups based on their gestational weight gain. Maternal, perinatal, and neonatal factors were analyzed, and early motor development was assessed using the Alberta infant motor scale (AIMS). RESULTS: EGWG was significantly associated with: pre-pregnancy BMI (p < 0.001), family history for cardiovascular diseases (p = 0.013) and diabetes mellitus (p = 0.045), hypertensive disorder of pregnancy (p = 0.003), gestational diabetes mellitus (p < 0.001), gestational anemia (p = 0.001), vitamin D deficiency (p = 0.001), metformin use (p = 0.045), pre-labor premature rupture of membranes (p = 0.031), amniotic fluid index (p = 0.047), and APGAR score in the first five min of life (p = 0.007). Scored by AIMS, EGWG was significantly associated with parameters of early motor development at the age of three AIMS total (p < 0.001), six AIMS total (p < 0.001), nine AIMS total (p < 0.001), and twelve AIMS total (p < 0.001) months of infant's life. CONCLUSIONS: The link between EGWG and adverse neurodevelopmental outcomes in offspring is a complex and multifaceted issue. Our results imply significant alterations in early motor development in the group of infants born from mothers who gained weight excessively during pregnancy. Further studies are needed to unravel the intricacies of this relationship and inform strategies for preventive interventions and supportive care during pregnancy and infancy.

Understanding the Dynamics of Human Papillomavirus and Diagnostic Discrepancies in Cervical Pathology: A Single Center Experience.

Cervical cancer (CC) is the most prevalent gynecological malignancy and a leading cause of death among women. It is primarily caused by human papillomavirus (HPV) infection, with 99.7% of cases showing high-risk HPV genotypes. This study sheds light on HPV dynamics as well as the discrepancies of different CC screening modalities results while highlighting factors that may have contributed to such a scenario. Moreover, we underscore the importance of the non-viral etiology of CC as well. We examined the current trends of HPV infection and its effects on cervical health in women treated at a tertiary care center in Belgrade, Serbia. Patients with abnormal colposcopy findings like dysplasia and re-epithelization were more likely to test negative for HPV (p < 0.001). Interestingly, women with a positive Pap smear tested HPV negative significantly more often (p = 0.041). Finally, HPV-positive individuals were more likely to have CIN I and II histologies (p < 0.001), while CIN III occurred equally in women with and without the virus. It may be inferred that inconsistencies in detecting HPV and the presence of cervical lesions may eventually result in adjustments to screening guidelines, as is crucial to adopt a meticulous approach to promote periodical CC screening, as initial samples may test negative for HPV.

Isolated Deep Infiltrating Endometriosis of the Sciatic Nerve: A Case Report and Overview of the Literature.

Isolated deep infiltrating endometriosis (DIE) of sacral nerve roots or major pelvic nerves, including the sciatic nerve, is considered to be extremely rare. Due to the overlap with sciatica symptoms, the diagnosis of sciatica DIE is difficult yet crucial, as it results in permanent neural damage if left untreated. We report a case of a 45-year-old woman who experienced a three-year-long and recently exacerbating pain in her right leg, accompanied by a tingling sensation and weakness in her right leg and foot, with difficulty walking. In between regular menstrual bleedings, when her aforementioned symptoms worsened, she had been experiencing mild 10-day extra-cyclical bleeding. Her neurologist's, orthopedist's, and gynecological examinations were unremarkable. Magnetic resonance imaging (MRI) showed an infiltrative lesion on the right sciatic nerve that was immunohistochemically confirmed to be endometriosis. The patient was treated with gonadotropin-releasing hormone analogues (GnRHa), which led to a significantly diminished size of the lesion on the control MRI, and endometriosis remission was obtained. For persistent mild, but cyclical, pain and muscle weakness, continuous progestagnes were administered, with advice for physical therapy provided for her neuro-muscle rehabilitation and a scheduled check-up in 6 months.

Stroke vs. Preeclampsia: Dangerous Liaisons of Hypertension and Pregnancy.

Stroke during pregnancy and preeclampsia are two distinct but interrelated medical conditions, sharing a common denominator-blood control failure. Along with cardiovascular diseases, diabetes, dyslipidemia, and hypercoagulability, hypertension is undoubtedly a major risk factor associated with stroke. Even though men have higher age-specific stroke rates, women are facing higher life-long stroke risk, primarily due to longer life expectancy. Sex hormones, especially estrogen and testosterone, seem to play a key link in the chain of blood pressure control differences between the genders. Women affected with stroke are more susceptible to experience some atypical stroke manifestations, which might eventually lead to delayed diagnosis establishment, and result in higher morbidity and mortality rates in the population of women. Preeclampsia is a part of hypertensive disorder of pregnancy spectrum, and it is common knowledge that women with a positive history of preeclampsia are at increased stroke risk during their lifetime. Preeclampsia and stroke display similar pathophysiological patterns, including hypertension, endothelial dysfunction, dyslipidemia, hypercoagulability, and cerebral vasomotor reactivity abnormalities. High-risk pregnancies carrying the burden of hypertensive disorder of pregnancy have up to a six-fold higher chance of suffering from stroke. Resemblance shared between placental and cerebral vascular changes, adaptations, and sophisticated auto-regulatory mechanisms are not merely coincidental, but they reflect distinctive and complex cardiovascular performances occurring in the maternal circulatory system during pregnancy. Placental and cerebral malperfusion appears to be in the midline of both of these conditions; placental malperfusion eventually leads to preeclampsia, and cerebral to stoke. Suboptimal performances of the cardiovascular system are proposed as a primary cause of uteroplacental malperfusion. Placental dysfunction is therefore designated as a secondary condition, initiated by the primary disturbances of the cardiovascular system, rather than an immunological disorder associated with abnormal trophoblast invasion. In most cases, with properly and timely applied measures of prevention, stroke is predictable, and preeclampsia is a controllable condition. Understanding the differences between preeclampsia and stroke in pregnancy is vital for healthcare providers to enhance their clinical decision-making strategies, improve patient care, and promote positive maternal and pregnancy outcomes. Management approaches for preeclampsia and stroke require a multidisciplinary approach involving obstetricians, neurologists, and other healthcare professionals.

Four Waves of the COVID-19 Pandemic: Comparison of Clinical and Pregnancy Outcomes.

During the last two and a half years, clinical manifestations, disease severity, and pregnancy outcomes have differed among pregnant patients with SARS-CoV-2 infection. These changes were preceded by the presence of new variants of SARS-CoV-2, known in the literature as variants of concern. The aim of this study is to describe the differences between maternal clinical characteristics and perinatal outcomes among pregnant women with COVID-19 during four waves of the COVID-19 epidemic in Serbia. This retrospective study included a series of 192 pregnant patients who were hospitalized due to the severity of their clinical status of SARS-CoV-2 infection. During four outbreaks of COVID-19 infection in Serbia, we compared and analyzed three sets of variables, including signs, symptoms, and characteristics of COVID-19 infection, clinical endpoints, and maternal and newborn parameters. During the dominance of the Delta variant, the duration of hospitalization was the longest (10.67 ± 1.42 days), the frequency of stillbirths was the highest (17.4%), as well as the frequency of progression of COVID infection (28.9%) and the requirement for non-invasive oxygen support (37%). The dominance of the Delta variant was associated with the highest number of prescribed antibiotics (2.35 ± 0.28), the most common presence of nosocomial infections (21.7%), and the highest frequency of corticosteroid therapy use (34.8%). The observed differences during the dominance of four variants of concern are potential pathways for risk stratification and the establishment of timely and proper treatments for pregnant patients. Early identification of the Delta variant, and possibly some new variants with similar features in the future, should be a priority and, perhaps, even an opportunity to introduce more accurate and predictive clinical algorithms for pregnant patients.

The Translation and Cross-Cultural Adaptation of the Pregnancy Physical Activity Questionnaire: Validity and Reliability of a Serbian Version (PPAQ-SRB).

Exercise during pregnancy has a positive effect on the health of both pregnant women and their fetuses. This study aimed to translate the Pregnancy Physical Activity Questionnaire (PPAQ) into the Serbian language and assess its validity and reliability among Serbian pregnant women. The study was conducted between October 2020 and March 2021 at the Obstetrics and Gynecology Clinic (Narodni Front), in Belgrade, Serbia. The PPAQ was translated according to a standardized methodology, and its internal consistency and construct and concurrent validity were assessed. The mean PPAQ score for the total amount of physical activity was 37.72 MET-h/week-1. Exploratory factor analysis of the Serbian PPAQ identified six factors similar to the original questionnaire that explained 70.26% of the data variance. The Cronbach's alpha coefficient of the Serbian version of the PPAQ was 0.69. The two-week intraclass correlation coefficient (ICC) scores ranged from 0.768 to 0.930. We tested the evidence to assess the concurrent validity of the Serbian version of PPAQ (PPAQ-SRB) correlations with the International Physical Activity Questionnaire-long form (IPAQ-LF), and all domains of the PPAQ were significantly correlated with domains of the IPAQ-LF. The findings of our reliability and validity evaluation are consistent with those of prior studies, indicating that the PPAQ was successfully translated and implemented in the Serbian population and that its reliability was acceptable.

Analysis of essential, toxic, rare earth, and noble elements in maternal and umbilical cord blood.

Progressive industrialization in recent decades has contributed to the increase of metal levels in the environment, which has a dangerous impact on human health, primarily pregnant women. In this study, we aimed to compare levels of various elements in maternal and umbilical cord (UC) plasma samples collected from 125 healthy pregnant women, conduct correlation analysis among paired plasma samples, and compare our data with other populations worldwide. The study design included the following elements: essential (Mn, Co, Cu, Zn, Se, Mo), non-essential (Be, Al, Ni, As, Rb, Sr, Cd, Sb, Pb, U), rare earth (La, Pr, Ce, Nd, Sm, Eu, Gd, Dy, Ho, Er), and noble metals (Ru, Rh, Re, Pt). Levels of 30 elements were higher in maternal plasma than in UC plasma samples. However, no disparities at the statistically significant level were found for Be, Zn, Rb, Cd, Ce, and Ho. Correlation analysis among paired plasma samples revealed only positive/synergistic correlations of different strengths between most elements. Compared to other countries across the globe, our participants had considerably lower plasma levels of Zn and higher levels of Co, Ni, and As. This study provides not only a new and deeper comprehension, but also the first insight into the levels, correlation, distribution, and potential transplacental transfer of 30 elements.

Gestational Diabetes and Risk Assessment of Adverse Perinatal Outcomes and Newborns Early Motoric Development.

Background and Objectives: The aim of this study was to analyze the presence of gestational diabetes mellitus (GDM) on maternal and fetal perinatal parameters, as well to evaluate the influence of GDM on neonatal early motoric development. Materials and Methods: In this prospective study, we evaluated 203 eligible participants that were admitted to obstetrics department for a labor. GDM was assessed by evaluation of maternal parameters, fetal parameters, as well its impact on infants early motoric development (Alberta Infant Motor Scale-AIMS). Results: Presence of GDM was significantly positively associated with: pre-pregnancy weight, obesity degree, weight at delivery, gestational weight gain (GWG), body mass index (BMI) at delivery, GWG and increased pre-pregnancy BMI, glucose levels in mother's venous blood after the delivery, positive family history for cardiovascular disease, pregnancy-related hypertension, congenital thrombophilia, drug use in pregnancy, large for gestational age (LGA), mode of delivery (Cesarean section and instrumental delivery). Likewise, GDM association was detected for tested ultrasound parameters (biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femoral length (FL)), length at birth, birth weight, newborn's head circumference, newborn's chest circumference, AIMS supination and pronation at three months, AIMS supination, pronation, sitting and standing at six months. Only Amniotic Fluid Index and AIMS supination at three months of infant's age remained significantly associated in multivariate regression model. Conclusions: The presence of significant positive association of numerous tested parameters in our study on perinatal outcomes and early motoric development, points to the necessity of establishing appropriate clinical decision-making strategies for all pregnant woman at risk and emphasize the importance of providing adequate glycaemia control options and further regular follow ups during the pregnancy.

Human biomonitoring of essential, nonessential, rare earth, and noble elements in placental tissues.

Exposure to certain metals has been recognized as a risk factor for numerous complications in vulnerable population groups, particularly pregnant women. This investigation evaluated the levels of essential (Cr, Mn, Co, Cu, Zn, Se, Mo) and nonessential trace metals with recognized toxicity (Be, Al, Ti, V, Ni, Ga, As, Rb, Sr, Cd, Sb, Ba, Tl, Hg, Pb, Bi, Th, U), together with rare earth elements (Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Yb, Lu), and noble metals (Ru, Rh, Pd, Re, Os, Ir, Pt, Au, Ag) in the placental tissues of healthy pregnant women (n = 105). The selection of participants was undertaken with special reference to specific confounding factors that could influence the trace element profiles. Among trace elements, Zn was the most abundant and Lu was the least abundant. Cd and Os placental levels show a tendency to increase with women's age. Compared with literature data, high levels of Ni were found. This is the first study that provides the composition levels of essential and toxic trace elements, rare earth elements, and noble metals in human placental tissues. Also, for the first time, normal (reference) ranges for 50 (ultra)trace elements in placental tissues are proposed. Reference ranges are especially important in biomonitoring studies, which nowadays give increasing importance to the analysis of solid tissues instead of body fluids. Overall, the information provided in this study can serve as a starting point for further clinical trials and/or prediction of potential risks to pregnancy.

Oxidative Stress Profile in Genetically Confirmed Cases of Leber's Hereditary Optic Neuropathy.

The mechanisms of the complex pathophysiology of Leber's hereditary optic neuropathy (LHON) are still insufficiently clarified. The role of oxidative stress as an etiological factor has been proposed and demonstrated in vitro, but without conclusive data that rely on clinical samples. The aim of the study was to evaluate and characterize the existence of oxidative stress in the plasma of LHON patients and healthy individuals. Whole mitochondrial genome sequencing has been performed in order to identify primary LHON mutations. For the assessment of oxidative stress, the following biomarkers were determined in plasma: total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), while oxidative damage of cellular proteins was estimated by quantifying advanced oxidation protein products (AOPP). All three primary LHON mutations (m.3460G > A, m.11778G > A and m.14484 T > C) were identified as a genetic cause of the disease, where the most prevalent one was m.11778G > A. LHON patients have a highly significant increase of TOS and a marked decrease of TAS levels, which suggests the existence of substantial oxidative stress. OSI is high in LHON patients, which definitely implies the presence of redox imbalance. Elevated level of AOPP in LHON patients refers to the significant deleterious effects of oxidative stress on cellular proteins. Oxidative stress parameters do not significantly differ between LHON individuals with different primary mutations. Both symptomatic and asymptomatic LHON patients have an augmented level of oxidative stress which suggests that primary mutations exhibit a pro-oxidative phenotype. Gender and smoking habit significantly influence examined biochemical parameters when LHON patients are compared with the control group. Different mitochondrial haplogroups are characterized by altered levels of OSI in LHON group. The absence of physiological correlations between redox parameters reflects the deregulation of homeostatic oxidative/antioxidative balance in LHON patients. This is the greatest series of LHON patients that were evaluated for oxidative stress and the first case-controlled study that evaluated TOS, TAS, OSI, and AOPP and their influence on disease phenotype. It is evident that the presence of oxidative stress represents an important pathophysiological event in LHON and that it could potentially serve as a circulatory biomarker for a therapy efficacy understanding.

The Influence of Increased Prepregnancy Body Mass Index and Excessive Gestational Weight Gain on Pregnancy Course and Fetal and Maternal Perinatal Outcomes.

Background: The aim of our study was to assess the influence of prepregnancy Body Mass Index (BMI) changes as well as excessive gestational weight gain (GWG) on maternal and fetal perinatal parameters. Furthermore, we aimed to analyze the influence of increased prepregnancy BMI values and excessive GWG on neonatal early motoric development. Methods: The 203 eligible female participants were evaluated. Prepregnancy Body Mass Index (BMI) and excessive gestational weight gain (GWG) defined according to Institute of Medicine 2009 guidelines in the USA were assessed with tested maternal and fetal perinatal parameters and infants early motoric development (Alberta Infant Motor Scale-AIMS). Results: Significant predictors of increased prepregnancy BMI in perinatal period include: weight at delivery (p = 0.001), GWG (p = 0.002) and BMI at delivery (p < 0.001), while significant predictors of excessive GWG in perinatal period are: prepregnancy BMI (p = 0.029) and BMI at delivery (p < 0.001). In the group of participants with both increased prepregnancy BMI and excessive GWG versus others, significant predictors were: hypertension (HTA) (p = 0.019), amniotic fluid index (AFI) (p = 0.047), Pronation (AIMS) (p = 0.028) and Supination (AIMS) (p = 0.029). Conclusion: Increased prepregnancy BMI and excessive GWG are significantly associated with numerous perinatal factors that could alter the pregnancy course, pregnancy outcome and early motoric development of newborn. Moreover, increased prepregnancy BMI is shown to be a significant predictor of excessive GWG; thus, early selection of pregnant women for close monitoring of weight gain during pregnancy will have positive effects on reducing the risk of less favorable pregnancy course and early motoric development of newborn.

In silico model of mtDNA mutations effect on secondary and 3D structure of mitochondrial rRNA and tRNA in Leber's hereditary optic neuropathy.

The Leber's hereditary optic neuropathy (LHON) is a rare disease caused by mitochondrial DNA (mtDNA) mutations. Beside primary mutations, the effect of secondary mtDNA mutations in still unclear. We examined the effect of secondary mtDNA mutations on secondary structure of different mitochondrial RNAs. Whole mitochondrial genome sequence of LHON patients has been obtained from in six non related pedigrees by Sanger sequencing method. The effect of mutations located in mitochondrial RNA genes was examined by creating in silico models of RNA secondary and regional 3D structure, accompanied by sequence conservation analysis. All three primary LHON mutations (m.3460G>A, m.11778G>A and m.14484 T>C) were revealed in study families. Four mutations in MT-RNR1 gene (m.750A>G, m.956delC, m.1438A>G and m.1555A>G) were identified and only an m.1555A>G causes significant changes of secondary structure of mitochondrial 12S ribosomal RNA (rRNA), while it is the only mutation which does not alter its 3D structure. Five mutations (m.1811A>G, m.2706A>G, m.2831G>A, m.3010G>A and m.3197T>C) were discovered in MT-RNR2 gene and all of them induced substantial alterations of mitochondrial 16S rRNA secondary structure. Significant changes of mitochondrial 16S rRNA 3D structure are caused by m.1811A>G, m.2706A>G, m.3010G>A and m.3197T>C. A single insertion variant (m.15986insG) has been found in the MT-TP gene which encodes mitochondrial transfer RNA for Proline (tRNA Pro). This mutation does not cause substantial changes of tRNA for Proline secondary structure, while the 3D geometry remains without major changes. Most of the mutation loci exhibited high level of sequence conservation. Presence of multiple mutations in a single family appears to cause more extensive changes in mitochondrial 12S and 16S rRNA, then their individual influence. The effect of discovered mutations on in silico modelled RNA structure is in a significant correlation with the present knowledge about the potential of these mutation to participate in the pathophysiology of LHON and other human diseases. The presence of certain multiple mitochondrial RNA mutations could be a possible explanation of LHON clinical presentation in some families. All revealed mutations have been evaluated for the first time in terms of in silico structural modelling. The application of bioinformatics tools such as secondary and 3D RNA structure prediction can have a great advantage in better understanding of the molecular standpoint of the LHON pathophysiology and clinical phenotype.