The Role of Regulatory T Cells and Their Therapeutic Potential in Hypertensive Disease of Pregnancy: A Literature Review.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Healthy mothers with normal cardiotocograms at term. Is maternal age a true determinant of perinatal outcome?

OBJECTIVE: to study the true determinants of adverse perinatal outcome (APO) in term healthy mothers with normal cardiotocograph (CTG), evaluating the real influence of maternal age. MATERIAL AND METHODS: In a retrospective study, we assessed a group of 529 term healthy mothers with normal CTGs that regardless of maternal age, evolved spontaneously up to 41 ± 2 weeks. The result of the conservative management was evaluated by means of univariable and multivariable logistic regression analysis, determining the association of maternal age and other clinical and ultrasonographical parameters with APO. RESULT: In contrast with low CPR MoM (OR = 0.155, p = .014), induction of labor (OR = 2.273, p = .023) and low parity (OR = 0.494, p = .026), maternal age and birth weight centile did not prove to be true determinants of perinatal outcome. The multivariable model for prediction of APO using clinical parameters presented a sensitivity of 35% and 27% for a false positive rate of 10% and 5%, AUC 0.736 (95% CI 0.655-0.818), p < .0001). CONCLUSIONS: in healthy old mothers with normal CTGs at term, APO is determined by low CPR, the existence of labor induction and low parity, while no real influence was observed for maternal age, fetal smallness, and interval examination-delivery. These results do not support the current consensus on induction at earlier weeks to prevent adverse outcomes in all cases of advanced maternal age, advocating for a more individualized, customized, and less interventional management based on fetal hemodynamics.

Reference values of fetal ultrasound biometry: results of a prospective cohort study in Lithuania.

PURPOSE: The aim of the study was to construct a reference range for the Lithuanian population for fetal biparietal diameter (BPD), occipitofrontal diameter (OFD), head circumference (HC), abdominal circumference (AC) and femur length (FL) and to compare them with the old local and current international reference values. METHODS: A prospective cross-sectional study was carried out in secondary referral centres Vilnius University Hospital Santariskiu Klinikos Centro Affiliate in 2008-2009 and Vilnius Maternity Hospital in 2009-2014. The fetal biometry of 556 fetuses between 12 and 42 weeks gestation was performed. BPD, OFD, HC, AC and FL were measured. The data were collected and the analysis was performed using statistical programs MS Excel, SPSS and Matlab. Different regression models were fitted to calculate the mean and standard deviation at each gestational age for each parameter. RESULTS: The biometric measurements of HC, BPD, OFD as well as AC and FL were performed for 556 fetuses. The centile charts, tables and regression formulae of the biometric parameters were constructed. The comparison of the current charts with those of other two studies revealed no significant differences of HC centiles. AC values were similar to those presented in the international study INTERGROWTH-21 and significantly higher in comparison to the study for the Lithuanian population conducted by Alisauskas (1980). FL values, especially in late pregnancy, were significantly smaller in the INTERGROWTH-21 study compared to our charts; however, there were no significant differences of the 50th centile compared to the results from Alisauskas. CONCLUSIONS: We have constructed and presented centile charts, tables and regression formulae for fetal biometry for the Lithuanian population and compared them with the results of two other studies. The significant differences between our centile charts and those from INTERGROWTH-21 imply the necessity to have local standards of fetal biometry, while the differences of our results from the older study in the same population show the importance of updating fetal biometry reference charts for every generation.

Congenital knee dislocation, case report and review of the literature.

Congenital dislocation of the knee (CDK) is characterized by hyperextension of the knee with forward displacement of the proximal tibia. It is associated with other joint dislocations and deformities and may occur isolated or as part of different systemic syndromes. Despite its characteristic postnatal morphology, prenatal descriptions are very scarce. We report a case of CDK diagnosed at 20 weeks, discuss its physiopathology, diagnosis and management and review the current literature.

Sirenomelia, case report and review of the literature.

We present a case of sirenomelia diagnosed in the first trimester of pregnancy. The ultrasound examination showed fused lower extremities and an anechoic structure in the lower abdomen that is clue in the early diagnosis. The postmortem study showed the existence of a single umbilical artery (vitelline artery), with an origin in the abdominal aorta. This finding not only explained the presence of a vascular steal with subsequent underdeveloped of pelvic organs, but also differentiated this condition from caudal regression syndrome.

Association of first trimester fetal heart rate and nuchal translucency with preterm birth.

OBJECTIVE: To evaluate whether first trimester fetal heart rate (FHR) and nuchal translucency (NT) associate with preterm birth (PTB). METHODS: This was a comparative case-control study of 518 normal pregnancies with no history of PTB, of which 272 delivered at term (TB) and 246 progressed to spontaneous PTB prior to 37, 34, 32, and 28 weeks. Fetal heart rate (FHR) and NT values at the first-trimester scan were compared by means of univariable (Mann-Whitney) and multivariable logistic regression analysis considering hourglass membranes (HM) as the most severe PTB subgroup. Finally, severity trends for both parameters were investigated using correlations with gestational age (GA) at delivery and Kruskal-Walls tests. RESULTS: Regardless of GA at delivery, pregnancies affected with PTB showed higher FHR and thicker NT at the first trimester scan. The association was confirmed by the multivariable analysis and the severity trends, which paired the highest FHR and NT values with the most severe cases of PTB (p < .001) (p < .0001). CONCLUSION: Fetuses with subsequent late, early and very early PTB show higher values of NT and FHR at the first-trimester scan.

Which is the best ultrasound parameter for the prediction of adverse perinatal outcome within 1 day of delivery?

OBJECTIVE: To compare the accuracies of several sonographic parameters for the prediction of adverse perinatal outcome (APO) prior to delivery. METHODS: This was a prospective study of fetuses attending the day hospital unit of a tertiary referral hospital that were scanned at 34-41 weeks and gave birth within 24 h of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH < 7.20 requiring urgent cesarean section, neonatal umbilical cord pH < 7.10, 5' Apgar score <7 and postpartum admission to neonatal or pediatric intensive care units. The accuracies of the middle cerebral, vertebral and umbilical arteries pulsatility index multiples of the median (MoM), the cerebroplacental and vertebroplacental ratios MoM and the EFW in centiles for the prediction of APO was evaluated by means of ROC curves and logistic regression analysis. RESULTS: A total of 2140 fetuses were prospectively scanned, however only 182 entered into spontaneous or induced labor and were delivered within 24 h of examination. In this group, MCA PI MoM was the best predictor of APO (AUC = 0.76, 95% CI 0.66-0.85, p < .0001) followed by the CPR MoM (AUC = 0.73, 95% CI 0.63-0.84, p < .0001) and the VPR MoM (AUC = 0.71, 95% CI 0.61-0.81, p < .001). Logistic regression analysis indicated that MCA PI MoM was the only independent determinant for the prediction of APO. CONCLUSION: In a high-risk population of third-trimester fetuses delivering within 24 h of examination, the outcome may be moderately anticipated just with the information provided by the cerebral flow.

The Diagnostic Ability of the Cerebroplacental Ratio for the Prediction of Adverse Perinatal Outcome and Intrapartum Fetal Compromise within One Day of Delivery.

OBJECTIVES: The objectives of this study were to evaluate the diagnostic abilities of the cerebroplacental ratio (CPR) for the prediction of adverse perinatal outcome (APO) and cesarean section for intrapartum fetal compromise (CS-IFC) within 1 day of delivery. DESIGN: Retrospective observational case-control study. METHODS: This was a study of 254 high-risk fetuses attending the day hospital unit of a tertiary referral hospital that underwent an ultrasound examination at 32-41 weeks and gave birth within 1 day of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section, neonatal umbilical cord pH <7.10, 5-min Apgar score <7, and postpartum admission to neonatal or pediatric intensive care units. CS-IFC was defined in case of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section. The diagnostic ability of CPR for the prediction of APO and CS-IFC was calculated alone and in combination with estimated fetal weight and gestational clinical parameters, including the type of labor onset, using ROC curves and logistic regression analysis. RESULTS: CPR in multiples of the median (MoM) was a moderate predictor of APO (area under the curve [AUC] = 0.77, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001). The predictive abilities of the multivariable model for APO (AUC = 0.81, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001) did not differ from those of CPR alone . LIMITATIONS: The small number of cases and the scarcity of information concerning labor induction. CONCLUSION: In high-risk pregnancies, CPR MoM is a moderate predictor of APO and CS-IFC when performed within 24 h of delivery.

Predictors of exclusive breastfeeding in the first six months: four consecutive surveys in a tertiary hospital in Lithuania.

BACKGROUND: There are little up-to-date data available on the duration of exclusive breastfeeding in Lithuania. The aim of our study was to examine the factors that could influence exclusive breastfeeding during the first 6 months of life. METHODS: In 2016, a survey was conducted at the Obstetrics and Gynecology Clinic of Vilnius University Hospital, Santaros Klinikos. Women in postnatal wards were opportunistically offered questionnaires and later followed up by telephone interviews at 6 weeks, 3 months, and 6 months postpartum. We used binary logistic regression to determine the factors that impacted exclusive breastfeeding during the first 6 months following childbirth. RESULTS: Of 475 eligible women that were approached, a total of 447 women were recruited, with response rates of 76.1, 71.4 and 67.0% at 6 weeks, 3 months, and 6 months postpartum, respectively. The prevalence of exclusive breastfeeding through the 6 month postpartum period was 39.8%. Exclusive breastfeeding during days 2 to 4 postpartum was positively influenced by factors such as a natural childbirth, the practice of breastfeeding on demand and maternal self-confidence in breastfeeding. Subsequently, exclusive breastfeeding on demand in the immediate postpartum period and exclusive breastfeeding for up to 3 months were associated with successful exclusive breastfeeding up to 6 months. However, the adverse factors that limited the success and duration of exclusive breastfeeding included free samples of human milk substitutes or advertising at primary healthcare centers 6 weeks after childbirth, pacifier use 6 months after childbirth, as well as amniotomy for labor induction. CONCLUSIONS: Our research demonstrated that exclusive breastfeeding is impacted in both directions by a range of factors during particular periods after delivery. One of the novel findings was the adverse influence of amniotomy for labor induction on exclusive breastfeeding rates. Taking into account diverse factors influencing exclusive breastfeeding and the absence of a single way to promote it, there is a crucial need to increase the incidence of exclusive breastfeeding until infants reach the age of 6 months.

MicroRNA-148b-3p and MicroRNA-25-3p Are Overexpressed in Fetuses with Late-Onset Fetal Growth Restriction.

OBJECTIVE: It was the aim of this study to describe a micro-RNA (miRNA) profile characteristic of late-onset fetal growth restriction (FGR) and to investigate the pathways involved in their biochemical action. METHODS: In this prospective study, 25 fetuses (16 normal and 9 with FGR [estimated fetal weight <10th centile plus cerebroplacental ratio <0.6765 multiples of the median]) were evaluated with Doppler ultrasound after 36 weeks. Afterwards, for every fetus, plasma from umbilical vein blood was collected at birth, miRNA was extracted, and full miRNA sequencing was performed. Subsequently, comparisons were done in order to obtain those miRNAs that were differentially expressed. RESULTS: The FGR fetuses expressed upregulation of two miRNAs: miR-25-3p and, especially, miR-148b-3p, a miRNA directly involved in Schwann cell migration, neuronal plasticity, and energy metabolism (p = 0.0072, p = 0.0013). CONCLUSIONS: FGR fetuses express a different miRNA profile, which includes overexpression of miR-25-3p and miR-148b-3p. This information might improve our understanding of the pathophysiological processes involved in late-onset FGR. Future validation and feasibility studies will be required to propose miRNAs as a valid tool in the diagnosis and management of FGR.

Reasons for Breastfeeding Cessation in the First Year after Childbirth in Lithuania: A Prospective Cohort Study.

Objectives: to identify the main reasons of breastfeeding cessation in Lithuania and if there is a link between the length of maternity leave and breastfeeding cessation. Methods: a prospective questionnaire study was conducted in a tertiary hospital from 2016 to 2017. The sample size included 449 women. Results: a total of 41% (n = 123) of respondents weaned off by 6 months after birth, and 57.8% (n = 173) between 6 months and 1 year. During the first few days after delivery, mothers did not breastfeed their infants mainly due to shortage of milk (n = 10; 40%) or separation from their baby due to infant health problems (n = 12; 48%) (p < 0.0001). Mothers who did not breastfeed during the first days after birth more often did not start breastfeeding later at home (p = 0.001). Going back to work was not a significant factor in weaning off. Conclusions: breastfeeding initiation and practice during the first few days after birth has a significant impact on the further commitment for full breastfeeding. Additionally, a perceived lack of support and help from both doctors and midwives influences a woman's decision to choose not to breastfeed.

Individual variability in height tracking in infancy: comparison of two longitudinal data sets of children born in 1990 and 1996 in Vilnius, Lithuania.

ABSTRACT: The aim of this study was to investigate variability of individual trajectories for height in two different birth cohorts of Lithuanian infants. Data were derived from the personal health records of 781 (399 boys and 382 girls) and 263 (139 boys and 124 girls) children born in 1990 and 1996 (respectively) in the city of Vilnius in Lithuania. The height of each child at birth, at one year and two years of age was investigated. The analysis of growth tracking was performed tracing the main centiles for height (3, 10, 25, 50, 75, 90 and 97). According to increase of height along the main centiles, five types of growth curves were possible. The average number of changed centile tracks for height for girls born in 1990, girls born in 1996 and boys born in 1996 was 2.05 ± 1.12, 2.02 ± 1.25 and 2.03 ± 1.06, respectively. However, the average number of changed centile tracks for height for boys born in 1990 was 1.74 ± 1.16, which differed significantly (p < 0.001) from the average number of changed centile tracks for height for girls born in 1990 and 1996, and boys born in 1996. Statistically significant differences (p < 0.001) were obtained between the incidences of the stable type of growth curve: the boys born in 1996 have presented the aforementioned type of growth curve much rarer compared to both the girls born in the same year and the boys born in 1990.