Unravelling the genetic landscape of cervical insufficiency: Insights into connective tissue dysfunction and hormonal pathways.

BACKGROUND: The intricate molecular pathways and genetic factors that underlie the pathophysiology of cervical insufficiency (CI) remain largely unknown and understudied. METHODS: We sequenced exomes from 114 patients in Latvia and Lithuania, diagnosed with a short cervix, CI, or a history of CI in previous pregnancies. To probe the well-known link between CI and connective tissue dysfunction, we introduced a connective tissue dysfunction assessment questionnaire, incorporating Beighton and Brighton scores. The phenotypic data obtained from the questionnaire was correlated with the number of rare damaging variants identified in genes associated with connective tissue disorders (in silico NGS panel). SKAT, SKAT-O, and burden tests were performed to identify genes associated with CI without a priori hypotheses. Pathway enrichment analysis was conducted using both targeted and genome-wide approaches. RESULTS: No patient could be assigned monogenic connective tissue disorder neither genetically, neither clinically upon clinical geneticist evaluation. Expanding our exploration to a genome-wide perspective, pathway enrichment analysis replicated the significance of extracellular matrix-related pathways as important contributors to CI's development. A genome-wide burden analysis unveiled a statistically significant prevalence of rare damaging variants in genes and pathways associated with steroids (p-adj = 5.37E-06). Rare damaging variants, absent in controls (internal database, n = 588), in the progesterone receptor (PGR) (six patients) and glucocorticoid receptor (NR3C1) (two patients) genes were identified within key functional domains, potentially disrupting the receptors' affinity for DNA or ligands. CONCLUSION: Cervical insufficiency in non-syndromic patients is not attributed to a single connective tissue gene variant in a Mendelian fashion but rather to the cumulative effect of multiple inherited gene variants highlighting the significance of the connective tissue pathway in the multifactorial nature of CI. PGR or NR3C1 variants may contribute to the pathophysiology of CI and/or preterm birth through the impaired progesterone action pathways, opening new perspectives for targeted interventions and enhanced clinical management strategies of this condition.

Human Leucocyte Antigen Class II Risk and Protective Alleles in Women with Cervical Intraepithelial Neoplasia.

Background: Persistent human papillomavirus (HPV) infection is a necessary cause for development of cervical precancerous lesions and cervical cancer, however, only a small percentage of women progress to cervical cancer. The local immune response, determined, among other factors, by Human Leucocyte Antigen (HLA) genes, is thought to be significant. Still the results of genome studies are inconsistent and differ between ethnical populations. The aim of the study was to assess an association between HLA-DQA1*; DQB1*; DRB1* allele's genetic variants between women with cervical precancerous lesions and healthy controls in Latvia. Materials and methods: From January until April 2017 we enrolled 84 consecutive patients referred for colposcopy to Riga East University Hospital (Latvia) due to abnormal cervical cytology results. 57 women who came for a regular check-up and had normal cytology smears were included in the control group. Material from the cervix was taken for subsequent HLA genotyping of 13 DRB1*, 8 DQA1*, and 12 DQB1* alleles. Colposcopy was performed on all participants. In case of visual suspicion for CIN cervical biopsy was done. Results: There were 57 "no CIN" patients, 23 histologically proven CIN 1 and 61 CIN2+ cases in the study population. CIN2+ was more often associated with DQA1*0401 (OR 6.68, 95% CI 1.47-30.29, p=0.014), DRB*15 (OR 2.99, 95% CI 1.22-7.39, p=0.017), DQB1*0401 (OR 2.91, 95%CI 1.11-7.68, p=0.03), DQA1*0103 (OR 2.72, 95% CI 1.02-7.21, p=0.045), DRB1*11 (OR 2.42, 95% CI 1.10-5.33, p=0.029) and DQB1*0301 (OR 1.94, 95% CI 1.12-3.38, p=0.018). Women with "no CIN" more often had DQB1*0501 (OR 0.17, 95% CI 0.04-0.81, p=0.026), DRB1*16 (OR 0.21, 95% CI 0.06-0.78, p=0.019), DQA1*0301 (OR 0.35, 95% CI 0.14-0.87, p=0.024) and DRB1*14 (OR 0.59, 95% CI 0.01-0.46, p=0.007). Conclusions: In the current study we have demonstrated a strong association with risk and protective HLA class II alleles that are determined by the HLA-DRB1*; DQA1*; DQB1*.

In-Depth Analysis of Caesarean Section Rate in the Largest Secondary Care-Level Maternity Hospital in Latvia.

There is no surgical intervention without risk. A high rate of caesarean sections (CSs) impacts on maternal and newborn mortality and morbidity. For optimisation of the CS rate, regular monitoring is necessary. In 2015, the World Health Organization recommended the Robson classification as a global standard for assessing, monitoring, and comparing CS rates. We analysed all births in 2019 in the Riga Maternity Hospital-a secondary-level monodisciplinary perinatal care hospital in Latvia-according to the Robson classification, seeking to identify which groups make the biggest contribution to the overall CS rate. In total, 5835 women were included. The overall CS rate was 21.5%. In our study, the largest contributors to the overall CS rate were as follows: Group 5 (33.3%); Group 2 (20.8%); and Group 1 (15.6%). The results of our deeper analysis of individual groups (Group 1 and 5) from our study may help to develop targeted interventions for specific subgroups of the obstetric population, effectively reducing both the overall rate of CS and the number of unnecessary CSs performed. The CS rate reduction strategy should be based on decreasing CSs in Group 1 and encouraging VBAC, thus decreasing the number of women undergoing two or more CSs in future.

Impact of Intraoperative Factors on the Development of Postpartum Septic Complications.

Background and Objectives: Triclosan-coated sutures (antibacterial sutures) can reduce the risk of postoperative surgical site infection. This study aimed to investigate the effect of intraoperative factors, including antibacterial sutures, on the risk of postpartum septic complications. Materials and Methods: The prospective study included patients who underwent caesarean section. The exclusion criterion was chorioamnionitis. The investigation group patient's (n = 67) uterus and fascial sheath of the abdominal wall were sutured with triclosan-coated polyglactin 910 sutures during surgery. The control group consisted of 98 patients using uncoated polyglactin 910 sutures only. The patients were contacted by phone after the 30th postoperative day. Results: No significant difference was found between the investigation group and the control group in the development of postpartum endometritis (11.7% in the investigation group vs. 8.4% in the control group, p = 0.401), wound infection (6.3% vs. 3.6%, p = 0.444) or patients experienced any septic complication (15.9% vs. 12%, p = 0.506). Postpartum endometritis was more common in patients who underwent instrumental uterine examination during the surgery (23.8% vs. 18%, p = 0.043). A moderately strong correlation was found for haemoglobin level on the third-fourth postoperative day with the development of postpartum septic complications, p < 0.001, Pearson coefficient -0.319. Post-caesarean delivery septic complications were not statistically more common in patients with blood loss greater than 1 L. The incidence of post-caesarean endometritis was 13.4%, and wound infection was 4.8% in this study's hospital, having five to six thousand deliveries per year. Conclusions: Using antibacterial sutures during caesarean section does not affect the incidence of postpartum septic complications. Instrumental uterine examination during caesarean section increases the risk of post-caesarean endometritis and is, therefore, not recommended. Haemoglobin level on the 3rd-4th postoperative day, rather than the estimated blood loss during surgery, affects the development of postpartum septic complications.

Management of Pregnancy with Cervical Shortening: Real-Life Clinical Challenges.

Background and Objectives: Preterm birth is the leading cause of neonatal mortality worldwide and may be responsible for lifelong morbidities in the survivors. Cervical shortening is one of the common pathways to preterm birth associated with its own diagnostic and management challenges. The preventive modalities that have been tested include progesterone supplementation and cervical cerclage and pessaries. The study aimed to assess the management strategies and outcomes in a group of patients with a short cervix during pregnancy or cervical insufficiency. Materials and Methods: Seventy patients from the Riga Maternity Hospital in Riga, Latvia, were included in the prospective longitudinal cohort study between 2017 and 2021. Patients were treated with progesterone, cerclage, and/or pessaries. The signs of intra-amniotic infection/inflammation were assessed, and antibacterial therapy was given when the signs were positive. Results: The rates of PTB were 43.6% (n = 17), 45.5% (n = 5), 61.1% (n = 11), and 50.0% (n = 1) in progesterone only, cerclage, pessary, and cerclage plus pesssary groups, respectively. The progesterone therapy was associated with a reduced preterm birth risk (x2(1) = 6.937, p = 0.008)), whereas positive signs of intra-amniotic infection/inflammation significantly predicted the risk of preterm birth (p = 0.005, OR = 3.82, 95% [CI 1.31-11.11]). Conclusions: A short cervix and bulging membranes, both indicators of intra-amniotic infection/inflammation, are the key risk factors in preterm birth risk predictions. Progesterone supplementation should remain at the forefront of preterm birth prevention. Among patients with a short cervix and especially complex anamnesis, the preterm rates remain high. The successful management of patients with cervical shortening lies between the consensus-based approach for screening, follow-up, and treatment on the one side and personalising medical therapy on the other.

Individual and country-level variables associated with the medicalization of birth: Multilevel analyses of IMAgiNE EURO data from 15 countries in the WHO European region.

OBJECTIVE: To investigate potential associations between individual and country-level factors and medicalization of birth in 15 European countries during the COVID-19 pandemic. METHODS: Online anonymous survey of women who gave birth in 2020-2021. Multivariable multilevel logistic regression models estimating associations between indicators of medicalization (cesarean, instrumental vaginal birth [IVB], episiotomy, fundal pressure) and proxy variables related to care culture and contextual factors at the individual and country level. RESULTS: Among 27 173 women, 24.4% (n = 6650) had a cesarean and 8.8% (n = 2380) an IVB. Among women with IVB, 41.9% (n = 998) reported receiving fundal pressure. Among women with spontaneous vaginal births, 22.3% (n = 4048) had an episiotomy. Less respectful care, as perceived by the women, was associated with higher levels of medicalization. For example, women who reported having a cesarean, IVB, or episiotomy reported not feeling treated with dignity more frequently than women who did not have those interventions (odds ratio [OR] 1.37; OR 1.61; OR 1.51, respectively; all: P < 0.001). Country-level variables contributed to explaining some of the variance between countries. CONCLUSION: We recommend a greater emphasis in health policies on promotion of respectful and patient-centered care approaches to birth to enhance women's experiences of care, and the development of a European-level indicator to monitor medicalization of reproductive care.

Women's perspectives on the quality of maternal and newborn care in childbirth during the COVID-19 pandemic in Latvia: Results from the IMAgiNE EURO study on 40 WHO standards-based quality measures.

OBJECTIVE: To investigate women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth during the COVID-19 pandemic in Latvia, comparing the years 2020 and 2021, among women who went into labor or had a prelabor cesarean. METHODS: Women giving birth in healthcare facilities in Latvia from March 1, 2020, to October 28, 2021, answered an online questionnaire including 40 WHO standards-based quality measures. Descriptive and multivariate quantile regression analyses were performed to compare QMNC in 2020 and 2021. RESULTS: 2079 women were included in the analysis: 1860 women who went into labor (group 1) and 219 with prelabor cesarean (group 2). Among group 1, 66.4% (n = 99/149) of women received fundal pressure in an instrumental vaginal birth, 43.5% (n = 810) lacked involvement in choices, 17.4% (n = 317) reported suffering abuse, 32.7% (n = 609) reported inadequate breastfeeding support while 5.2% (n = 96) lack of early breastfeeding. A significant reduction in QMNC due to the COVID-19 pandemic was reported by 29.5% (n = 219) and 25.0% (n = 270) of respondents in 2020 and 2021, respectively (P = 0.045). Multivariate analyses highlighted a significantly lower QMNC index for 2020 compared with 2021 (P < 0.001). CONCLUSION: This first study investigating QMNC in Latvia showed significant gaps in QMNC perceived by respondents, with slightly better results in 2021. Appropriate healthcare strategies to improve health care for women and newborns in Latvia are required. CLINICALTRIALS: gov Identifier:NCT04847336.

Iron Status in Pregnant Women in Latvia: An Epidemiological, Cross-Sectional, Multicenter Study According to WHO and UK Criteria.

Background and Objectives: During pregnancy, iron deficiency anaemia is a common problem associated with health risks for both the mother and her foetus/infant. This study aimed to investigate the prevalence of iron deficiency, iron deficiency anaemia, and related dietary patterns in pregnant women in Latvia. Materials and Methods: This cross-sectional, multicentre study included pregnancy data from 974 women. The sample selection was based on the stratification principle (population of women of childbearing age in regions of Latvia). Maternal demographic details, anthropometric measurements, iron status, dietary patterns, and supplementation information were obtained from maternal files and during interviews held in eight outpatient departments of medical institutions and maternity departments. The prevalence was assessed. Chi-square tests and logistic regression were used to identify associations between iron deficiency and sociodemographic characteristics, dietary patterns, and iron supplement intake during pregnancy. The criterion used for the diagnosis of iron deficiency anaemia is a Hb level <110 g/L in the 1st and 3rd trimesters and <105 g/L during the 2nd trimester as recommended by the WHO. However, the UK guideline was used for borderline iron deficiency, which is an SF level <30 µg/L in all trimesters. Results: The observed prevalence of anaemia was 2.8% in the first trimester, 7.9% in the second trimester, and 27.0% in the third trimester. The prevalence of iron deficiency was 46.7% in the first trimester, 78.1% in the second trimester, and 91.7% in the third trimester. No associations with dietary patterns were found. Single women had 1.85 times the odds (95% CI 1.07 to 3.18) of being anaemic than married women. Conclusions: Iron deficiency affects a large proportion of pregnant women in Latvia in all trimesters, with iron deficiency anaemia affecting pregnant women in the third trimester. Monitoring and intervention should be performed in a timely and more targeted manner.

Ultrasound Simulation for Training Trainees when the Luxury Becomes Essential: Opinion and Evidence Obtained during the Latvian Research Council Project Implementation.

Background: Simulation as a proxy tool for conditional clinical training became a powerful technique for introducing trainees to the ultrasound imaging world, allowing them to become a trained sonographer taking into consideration different rates of progress in completing a specific task against the time and ensuring the long-lasting maintenance of the obtained practical skills. Adding a costly, but effective high-fidelity simulator to the residency program justified the expense, demonstrating efficiency of training for improving the clinical performance and confidence of trainees. Materials and methods: A pilot study in Riga Maternity Hospital within the framework of the study "Role of metabolome, biomarkers and ultrasound parameters in successful labor induction" (Fundamental and Applied Research Programme lzp-2021/1-0300) was performed between March 1st 2022 and 31st April 2022. A virtual-reality simulator (ScanTrainer, MedaphorTM, Cardiff, UK) was used with the teaching module for assessment of the uterine cervix. Five trainees in obstetrics and two young specialists included in the study. None of them had Fetal Medicine Foundation certificate of competence in the assessment of the uterine cervical lenght before. The time used on the simulator, the number of simulations and a mean confidence in cervical length assessment before and after simulation were recorded. Results: The study on assesment of uterine cervical lenght demonstrated statistically significant increase in confidence (p=0.008) and statistically significant decrease in time needed to complete correctly the same tasks for the trainees (p=0.008) that shows a positive learning curve over the time of training on ScanTrainer, Medaphor. Conclusions: The simple task allows to become a certified specialist in uterine cervical assessment in the short period of time. That support the productiveness of the simulation-based education. The training program should be updated taking into consideration simulation curriculum.

Assessment of Iodine and Selenium Nutritional Status in Women of Reproductive Age in Latvia.

Background and Objectives: Adequate dietary intake of iodine and selenium is essential during pregnancy. While iodine is vital for maternal thyroid function and fetal development, selenium contributes to the regulation of thyroid function and thyroid autoimmunity. This study aimed to assess the consumption of iodine- and selenium-containing products by women of reproductive age and the iodine and selenium nutritional status of pregnant women in Latvia. Materials and Methods: Population health survey (2010-2018) data were used to characterize dietary habits in women of reproductive age. Additionally, 129 pregnant women in the first trimester were recruited; they completed a questionnaire and were tested for thyroid function, urinary iodine concentration (UIC), and serum selenium and selenoprotein P levels. Results: The use of some dietary sources of iodine (e.g., milk and dairy products) and selenium (e.g., bread) has decreased in recent years. Less than 10% of respondents reported the use of iodized salt. The use of supplements has become more common (reported by almost 50% of respondents in 2018). Dietary habits were similar in pregnant women, but the use of supplements was even higher (almost 70%). Nevertheless, most supplements used in pregnancy had insufficient contents of iodine and selenium. Thyroid function was euthyreotic in all women, but 13.9% of participants had a thyroid peroxidase antibodies (TPO-ab) level above 60 IU/mL. The median UIC (IQR) was 147.2 (90.0-248.1) µg/gCr, and 52.8% of pregnant women had a UIC below 150 µg/gCr. The mean selenium (SD) level was 101.5 (35.6) µg/L; 30.1% of women had a selenium level below 80 µg/L. The median selenoprotein P level was 6.9 (3.1-9.0) mg/L. Conclusions: Iodine nutrition in Latvian population of pregnant women was near the lower limit of adequate and a third of the population had a selenium deficiency. Supplements were frequently used, but most did not contain the recommended amounts of iodine and selenium.

Aerobic Vaginitis-Underestimated Risk Factor for Cervical Intraepithelial Neoplasia.

The aim of this study is to analyse the association between vaginal microbiota and the histological finding of CIN. From July 2016 until June 2017, we included 110 consecutive patients with abnormal cervical cytology results referred for colposcopy to Riga East Clinical University Hospital Outpatient department in the study group. 118 women without cervical pathology were chosen as controls. Certified colposcopists performed interviews, gynaecological examinations and colposcopies for all participants. Material from the upper vaginal fornix was taken for pH measurement and wet-mount microscopy. Cervical biopsy samples were taken from all subjects in the study group and in case of a visual suspicion for CIN in the control group. Cervical pathology was more often associated with smoking (34.6% vs. 11.0%, p < 0.0001), low education level (47.2% vs. 25.5%, p = 0.001), increased vaginal pH (48.2% vs. 25.4%, p < 0.0001), abnormal vaginal microbiota (50% vs. 31.4%, p = 0.004) and moderate to severe aerobic vaginitis (msAV) (13.6% vs. 5.9%, p = 0.049) compared to controls. The most important independent risk factors associated with CIN2+ were smoking (OR 3.04 (95% CI 1.37-6.76), p = 0.006) and msAV (OR 3.18 (95% CI 1.13-8.93), p = 0.028). Bacterial vaginosis (BV) was found more often in CIN1 patients (8/31, 25.8%, p = 0.009) compared with healthy controls (8/118, 6.8%), or CIN2+ cases (8/79, 10.1%). In the current study msAV and smoking were the most significant factors in the development of CIN in HPV-infected women, especially high grade CIN. We suggest that AV changes are probably more important than the presence of BV in the pathogenesis of CIN and progression to cervix cancer and should not be ignored during the evaluation of the vaginal microbiota.

Post-reproductive aged women: a lost generation in the cervical cancer screening programme.

OBJECTIVES: The aims of the study were to find out why some post-reproductive aged women did not participate in the organised cervical cancer screening programme in Latvia and to clarify factors that would motivate them to take part. METHODS: A cross-sectional study was carried out between January and July 2017 among female patients in three general practitioner (GP) practices. GP practice nurses used the Latvian national health service database to identify women aged 25-70 who had not participated in the organised programme for the last 3 years. Participants were asked to complete a specially developed questionnaire. The results were then compared between three age groups: 25-34, 35-49 and 50-70 years. RESULTS: Included in the study were 523 out of 992 women who had not attended screening; 41% were in the age group 50-70 years. Post-reproductive aged women statistically significantly more often did not take part in the programme because of lack of time (26.4%), too great a distance to the gynaecology screening clinic (10.4%), lengthy appointment waiting time (8.5%) and a belief that a smear test was unnecessary for them (8.5%); 32.1% of women in this age group indicated that if the cervical screen could be carried out by their GP it would facilitate their participation in the programme. CONCLUSION: Post-reproductive aged women in Latvia often do not attend cervical cancer screening. Analysis of personal and organisational barriers confirmed that the involvement of GPs would encourage older women to participate in the organised screening programme.

Sphincter muscle activity before and after delivery: Does it depend on the type of birth?

AIM: There are ongoing discussions whether cesarean section is the safest mode of childbirth to prevent pelvic floor disorders. Pelvic floor electromyography (EMG) allows the analysis of external anal sphincter (EAS) function during voluntary contractions. The primary objective of this study was the evaluation of EMG amplitude of external anal sphincter in women who had vaginal delivery, compared to women who had cesarean section. The secondary objective was to evaluate the anal incontinence score changes before and after delivery between the groups, and to look for any relationship between the clinical and EMG findings. METHODS: Multichannel surface EMG was detected during maximal contractions in three sessions: (i) during pregnancy, (ii) 6 weeks after delivery and (iii) 1 year after delivery. Women were divided into two groups: cesarean section and vaginal delivery. RESULTS: External anal sphincter EMG amplitude decreases 6 weeks after vaginal deliveries from 10.1 to 8.6 µV with effect size of 0.4, but returns to baseline after 1 year. No differences were observed between groups in all other variables. CONCLUSION: No differences were observed after 1 year in EMG activity between the two groups; however, a slight decrease of sphincter muscle amplitude was noted 6 weeks after vaginal delivery. The delivery mode does not have effect on the EAS amplitude 1 year after delivery. Incontinence score slightly increased in both groups after delivery, with no significant differences between the two groups. No association was observed between the increase of incontinence score and the decrease of EMG signal amplitude.

Genetic landscape of preterm birth due to cervical insufficiency: Comprehensive gene analysis and patient next-generation sequencing data interpretation.

Preterm delivery is both a traumatizing experience for the patient and a burden on the healthcare system. A condition distinguishable by its phenotype in prematurity is cervical insufficiency, where certain cases exhibit a strong genetic component. Despite genomic advancements, little is known about the genetics of human cervix remodeling during pregnancy. Using selected gene approaches, a few studies have demonstrated an association of common gene variants with cervical insufficiency. However, until now, no study has employed comprehensive methods to investigate this important subject matter. In this study, we asked: i) are there genes reliably linked to cervical insufficiency and, if so, what are their roles? and ii) what is the proportion of cases of non-syndromic cervical insufficiency attributable to these genetic variations? We performed next-generation sequencing on 21 patients with a clinical presentation of cervical insufficiency. To assist the sequencing data interpretation, we retrieved all known genes implicated in cervical functioning through a systematic literature analysis and additional gene searches. These genes were then classified according to their relation to the questions being posed by the study. Patients' sequence variants were filtered for pathogenicity and assigned a likelihood of being contributive to phenotype development. Gene extraction and analysis revealed 12 genes primarily linked to cervical insufficiency, the majority of which are known to cause collagenopathies. Ten patients carried disruptive variants potentially contributive to the development of non-syndromic cervical insufficiency. Pathway enrichment analysis of variant genes from our cohort revealed an increased variation burden in genes playing roles in tissue mechanical and biomechanical properties, i.e. collagen biosynthesis and cell-extracellular matrix communications. Consequently, the proposed idea of cervical insufficiency being a subtle form of collagenopathy, now strengthened by our genetic findings, might open up new opportunities for improved patient evaluation and management.

Barriers and motivators for uptake of cervical cancer prevention strategies in Eastern Europe: the perspective from Latvia.

INTRODUCTION: The incidence of cervical cancer (CC) in eastern European countries is high; however, uptake of available prevention strategies is suboptimal. We explored knowledge, behaviors, and attitudes toward CC prevention strategies in Latvian women. METHODS: A mixed-methods study of Latvian women, consisting of surveys and semi-structured interviews, was conducted in Riga, Latvia in September and October 2015. RESULTS: Altogether, 158 surveys were completed and 10 interviews were conducted. In total, 87% (n = 135) had previously had a smear test, and 67% (n = 105) correctly identified that cervical cytology was performed to identify precancerous changes. The practice of annual gynecological checkups was prevalent, and many believed it to be synonymous with cervical screening. Detailed knowledge of human papillomavirus (HPV) infection and the HPV vaccine was deficient, although 73% (n = 115) and 70% (n = 90), respectively, claimed to have heard of them. Negative attitudes existed regarding the HPV vaccine due to fear of potential side effects. On learning that HPV was transmitted through sexual contact, the notion of testing positive for HPV was met with shame and embarrassment. CONCLUSIONS: A small proportion of Latvian women are over-screened, whereas many women remain unscreened. The main contributing factor for this was their poor understanding of the roles that cervical screening and HPV vaccination play in preventing CC.

Barriers to accessing adequate maternal care in Latvia: A mixed-method study among women, providers and decision-makers.

INTRODUCTION: Latvia has a high maternal mortality ratio compared to other European countries, as well as major inequities in accessing adequate maternal care. Adequacy refers to the extent to which services are safe, effective, timely, efficient, equitable and people-centred. This study aims to explore stakeholder views on access to adequate maternal care in Latvia and the extent to which there was consensus. METHODS: This mixed-method study is based on an online survey among women who recently gave birth, as well as interviews with healthcare providers and decision-makers. The data were analysed using the method of directed qualitative content analysis. The extent of stakeholder consensus was determined by studying five access-related aspects of maternal care: availability, adequacy, affordability, approachability and acceptability. FINDINGS: Our study identified barriers to accessing adequate maternal care related to availability (i.e. shortage of human resources, geographical distance) and appropriateness (i.e. inequalities in provider knowledge, care provision and use of clinical guidelines). Other challenges were related to providers' approaches towards women (i.e. communication) and, to a lesser extent, maternal care acceptance by women (i.e. health literacy). CONCLUSIONS: The barriers identified in our study highlight areas that should be addressed in future reforms of maternal care. These barriers also indicate the need for micro-level indicators that can facilitate a comprehensive evaluation of maternal care in Latvia and elsewhere.

Could the correct side of mediolateral episiotomy be determined according to anal sphincter EMG?

INTRODUCTION AND HYPOTHESIS: Mediolateral episiotomy is one of the most frequent surgical interventions performed in obstetrics. There is conflicting evidence as to whether mediolateral episiotomy reduces the risk of obstetric anal sphincter injuries (OASI). Recent studies suggest that functional asymmetry of pelvic floor innervation exists in healthy women and is strongly associated with postpartum incontinence when the trauma occurs on the dominant side of innervation. Mediolateral episiotomy is the most common cause of perineal trauma during delivery, and the surgical incision is usually performed on the mediolateral right side. Surface electromyography (EMG) has been recently applied in obstetrics for detecting electrical activity of the external anal sphincter (EAS). METHODS: Two hundred and forty-five pregnant nulliparous women at their second and third trimester of pregnancy were recruited, and EMG signals were detected using a multichannel cylindric anal probe. Measurements were repeated and compared 6-8 weeks after delivery on a subgroup of 167 women who were divided in two groups according to EMG amplitude asymmetry before delivery and two subgroups according to type of delivery: (1A) asymmetric left, episiotomy right; (1B) asymmetric left, other types of deliveries; (2A) asymmetric right, episiotomy right; (2B) asymmetric right, other type of deliveries. RESULTS: The reduction of EMG amplitude after right episiotomy was larger in women with right asymmetric sphincter compared with women with left asymmetry and women with other types of delivery. CONCLUSIONS: Prenatal EMG may be used to predict the impact of right-sided mediolateral episiotomy on EAS and perhaps also function following delivery.

Awareness of HPV infection and attitudes toward HPV vaccination among Latvian adolescents.

OBJECTIVE: To evaluate awareness of HPV and its vaccine among Latvian adolescents. METHODS: A cross-sectional survey was conducted in a 2-week period in September 2015 among 270 adolescents attending a secondary school in Riga, Latvia. All students present during sexual-health classes (grades 10-12 [aged 16-21 years]) were included. A self-administered paper-based survey assessed sociodemographic factors, sexual behaviours, smear history and knowledge of sexually transmitted infections, HPV and HPV vaccine knowledge, and sources of information. RESULTS: Overall, 121 surveys were completed (62 by male students and 59 by female students). Latvian adolescents lacked awareness of HPV: only 26 (21.5%) had heard of HPV (21 [35.6%] female students vs 5 [8.1%] male students; P<0.001) and 12 (9.9%) of the HPV vaccine. Eighty (66.1%) participants felt inadequately informed about HPV. However, the adolescents partook in high-risk behaviours: 70 (57.9%) students were sexually active, 26 (37.1%) of whom had already had three or more sexual partners. CONCLUSION: Despite the high prevalence of HPV in Latvia, poor knowledge about HPV infection among adolescents could explain low uptake of the HPV vaccine by this high-risk population. Therefore, educational strategies that highlight the consequences of HPV could promote acceptance of vaccination.

Expression of p63, p53 and Ki-67 in Patients with Cervical Intraepithelial Neoplasia.

OBJECTIVE: Cervical intraepithelial neoplasia (CIN) is a dysplastic process in cervical squamous epithelium and carries a risk of progression to cervical cancer. The aim of this study was to compare expression of three biomarkers named p53, p63 and Ki-67 in patients with various grades of cervical intraepithelial neoplasia and in a control group. MATERIAL AND METHOD: 58 patients were enrolled in the study. Each patient underwent a colposcopy-guided biopsy of the cervix. Immunostaining for markers (p53, p63 and Ki-67) was performed on tissue samples of normal cases (n=10), CIN I (n=20), CIN II (n=14), and CIN III (n=14). RESULTS: Our study showed a significant increase of the expression of the analyzed biomarkers in most patients with CIN III compared to CIN II and CIN I. Furthermore, p53 and p63 were significantly increased in CIN I compared to the control group. CONCLUSION: The expression of Ki-67, p63 and p53 differed between CIN I, CIN II and CIN III. p63 and p53 were reliable biomarkers to distinguish reactive changes from CIN I, while all three biomarkers (Ki-67, p53 and p63) had a high degree of sensitivity and specificity to distinguish between CIN III, CIN II and CIN I.

Iodine deficiency during pregnancy: a national cross-sectional survey in Latvia.

OBJECTIVE: Low iodine intake during pregnancy may cause thyroid dysfunction, which results in inadequate fetal brain development. In the absence of a universal salt iodization programme, we conducted a nationwide survey of iodine deficiency in pregnant women in Latvia. DESIGN: A countrywide twenty-cluster survey, with at least twenty women per cluster. Participants completed a questionnaire on dietary habits concerning iodine intake (n 739). Thyroid function (thyroid-stimulating hormone, free thyroxine and thyroperoxidase antibodies) was measured (n 550). Urinary iodine was measured using the ammonium persulfate method (n 696). SETTING: The survey was performed in all regions of Latvia during the spring and autumn seasons in 2013. SUBJECTS: Pregnant women (n 829). RESULTS: The median creatinine (Cr)-standardized urinary iodine concentration (UIC) was 80·8 (interquartile range (IQR) 46·1-130·6) µg/g Cr or 69·4 (IQR 53·9-92·6) µg/l during pregnancy, and 81% of pregnant women had UIC levels below the WHO recommended range of 150-250 µg/g Cr. The UIC was lowest during the first trimester of pregnancy, 56·0 (IQR 36·4-100·6) µg/g Cr, reaching higher concentrations of 87·5 (IQR 46·4-141·7) µg/g Cr and 86·9 (IQR 53·8-140·6) µg/g Cr in the second and third trimesters, respectively. Women taking supplements containing ≥150 µg iodine (6·8% of respondents) had non-significantly higher UIC than did women without supplementation (96·2 v. 80·3 µg/g Cr, respectively, P=NS). Thyroperoxidase antibody concentration did not correlate significantly with UIC: Spearman's ρ=-0·012, P=0·78. CONCLUSIONS: The median UIC indicates iodine deficiency in pregnant women in Latvia. Iodine supplementation (150 µg daily) and regular UIC monitoring should be suggested to overcome iodine deficiency and to reach the recommended levels without inducing autoimmune processes.