Health-related quality of life and satisfaction associated with 3-year use of a levonorgestrel 13.5 mg intrauterine device vs Nova T copper 380 mm2 intrauterine device: Results of a phase 4 randomized controlled trial.

OBJECTIVES: This study aimed to investigate the impact of levonorgestrel 13.5 mg and Nova T copper 380 mm2 intrauterine devices (LNG13.5-IUD and Cu380-IUD, respectively) on health-related quality of life (HRQoL) and the satisfaction with the method throughout 3 years of use. STUDY DESIGN: We conducted a single-center, evaluator-masked, randomized controlled trial to compare the bleeding profile of LNG13.5-IUD and Cu380-IUD users. Secondary objectives included HRQoL and satisfaction throughout the study. We used the validated questionnaire of the Spanish Society of Contraception (SEC-QoL), which evaluates social, sexual/psychological well-being, and menstrual/breast symptoms, to assess HRQoL and a 5-point Likert scale for satisfaction. RESULTS: These secondary outcomes were assessed in the whole population included in the study: 55 LNG13.5-IUD and 51 Cu380-IUD users. The mean overall SEC-QoL scores were similar at baseline (61.5 and 59.6, respectively; p = 0.570) and greater for LNG13.5-IUD after 3 years (69.2 vs 52.5, respectively; p = 0.002). All SEC-QoL domains scored also higher (p < 0.05 vs Cu380-IUD for all). At month 36, 20/30 (67%) and 8/28 (29%) users, respectively, had reached the MID (a 3.4-point increase) in SEC-QoL score (p = 0.004). At this time, 24/29 (82%) and 9/28 (32%) users, respectively, were "very satisfied" (p < 0.001). Willingness to continue the method was similar (22/28 [79%] vs 17/28 [61%] users, respectively; p = 0.170). CONCLUSIONS: Among the use of LNG13.5-IUD was associated with better HRQoL vs Cu380-IUD throughout the 3 years. Satisfaction with the method was higher with LNG13.5-IUD. IMPLICATIONS: People considering having an LNG13.5-IUD or a Cu380-IUD inserted may now benefit from the information regarding the impact of these devices on HRQoL and satisfaction with the method as reported in our study conducted in Spain.

Bleeding profile and safety of a levonorgestrel 13.5 mg intrauterine device versus Nova T copper 380 mm2 intrauterine device: Results of a 3-year, single-center, randomized phase 4 study.

OBJECTIVE: To assess the bleeding profiles of the levonorgestrel 13.5 mg intrauterine device (LNG13.5-IUD) and Nova T copper 380 mm2 IUD (Cu380-IUD). STUDY DESIGN: Single-center, evaluator-masked, randomized study conducted in women aged 18-45 years starting these methods. Primary outcomes were number of bleeding days, self-reported bleeding intensity, Pictorial Blood Assessment Chart (PBAC) score, and blood biochemical values at baseline, months 3, 6, 12, 24, and 36 per 90-day reference periods except for PBAC (months). Secondary objectives were presence/duration/intensity of dysmenorrhea and tolerability. RESULTS: We included 106 women aged 32.5 ± 6.7 years: 55 with LNG13.5-IUD and 51 with Cu380-IUD. Data for LNG13.5-IUD versus Cu380-IUD at baseline and month 36 (both respectively) were as follows: (1) median (25th; 75th percentile) number of bleeding days: 12 (9.0; 15.0) versus 12 (9.0; 15.0), p = 0.82, and 4 (0; 13.7) versus 15 (14.2; 20.0), p < 0.001; (2) mean bleeding intensity: 1.7 for both, p = 0.66, and 0.7 and 2.2, p < 0.001. Forty percent versus 0% presented with amenorrhea at month 36; (3) mean PBAC score (95% Confidence interval (CI): 50.7 (16.6; 84.7) versus 130.4 (95.7; 165.0) at month 1, and 7.9 (-26.7; 42.6) versus 126 (90.7; 161.2), p < 0.001; (4) median (25th; 75th percentile) ferritin levels (Ug/L) 33 (19; 53) versus 30 (19; 45), p = 0.70, and 59 (42; 84) versus 21 (8; 39). We did not observe changes or differences between groups in hemoglobin and hematocrit. The duration and intensity of dysmenorrhea were significantly lower with LNG13.5-IUD versus Cu380-IUD. Adverse events were those expected. CONCLUSIONS: LNG13.5-IUD is associated with a significant reduction in blood loss and dysmenorrhea compared with Cu380-IUD. IMPLICATIONS: Women eligible for a levonorgestrel 13.5 mg intrauterine device (IUD) or a copper 380 mm2 IUD should be informed of the differences in bleeding profiles-one of the main causes for IUD discontinuation-so they can compare this information against their bleeding expectations.

The Potential of Sewage Sludge to Predict and Evaluate the Human Chemical Exposome.

Chemicals are part of our daily lives, and we are exposed to numerous chemicals through multiple pathways. Relevant scientific evidence contributing to the regulation of hazardous chemicals require a holistic approach to assess simultaneous exposure to multiple compounds. Biomonitoring provides an accurate estimation of exposure to chemicals through very complex and costly sampling campaigns. Finding efficient proxies to predict the risk of chemical exposure in humans is an urgent need to cover large areas and populations at a reasonable cost. We conducted an exploratory study to characterize the human chemical exposome in maternal blood and placenta samples of a population-based birth cohort in Barcelona (2018-2021). Ultimate HRMS-based approaches were applied including wide-scope target, suspect, and nontarget screening. Forty-two chemicals were identified including pesticides, personal care products, or industrial compounds, among others, in the range of ng/mL and ng/g. In parallel, sewage sludge from the wastewater treatment plants serving the residence areas of the studied population were also screened, showing correlations with the type and concentrations of chemicals found in humans. Our findings were suggestive for the potential use of sewage sludge as a proxy of the human exposure and its application in early warning systems to prevent bioaccumulation of hazardous chemicals.

The Evolving Microbiome from Pregnancy to Early Infancy: A Comprehensive Review.

Pregnancy induces a number of immunological, hormonal, and metabolic changes that are necessary for the mother to adapt her body to this new physiological situation. The microbiome of the mother, the placenta and the fetus influence the fetus growth and undoubtedly plays a major role in the adequate development of the newborn infant. Hence, the microbiome modulates the inflammatory mechanisms related to physiological and pathological processes that are involved in the perinatal progress through different mechanisms. The present review summarizes the actual knowledge related to physiological changes in the microbiota occurring in the mother, the fetus, and the child, both during neonatal period and beyond. In addition, we approach some specific pathological situations during the perinatal periods, as well as the influence of the type of delivery and feeding.

Oxygen and lack of oxygen in fetal and placental development, feto-placental coupling, and congenital heart defects.

Low oxygen concentration (hypoxia) is part of normal embryonic development, yet the situation is complex. Oxygen (O2 ) is a janus gas with low levels signaling through hypoxia-inducible transcription factor (HIF) that are required for development of fetal and placental vasculature and fetal red blood cells. This results in coupling of fetus and mother around midgestation as a functional feto-placental unit (FPU) for O2 transport, which is required for continued growth and development of the fetus. Defects in these processes may leave the developing fetus vulnerable to O2 deprivation or other stressors during this critical midgestational transition when common septal and conotruncal heart defects (CHDs) are likely to arise. Recent human epidemiological and case-control studies support an association between placental dysfunction, manifest as early onset pre-eclampsia (PE) and increased serum bio-markers, and CHD. Animal studies support this association, in particular those using gene inactivation in the mouse. Sophisticated methods for gene inactivation, cell fate mapping, and a quantitative bio-reporter of O2 concentration support the premise that hypoxic stress at critical stages of development leads to CHD. The secondary heart field contributing to the cardiac outlet is a key target, with activation of the un-folded protein response and abrogation of FGF signaling or precocious activation of a cardiomyocyte transcriptional program for differentiation, suggested as mechanisms. These studies provide a strong foundation for further study of feto-placental coupling and hypoxic stress in the genesis of human CHD.

[Perinatal outcome and cardiac dysfunction in preterm growth-restricted neonates in relation to placental impairment severity]. / Resultados perinatales y disfunción cardiovascular en prematuros con restricción del crecimiento intrauterino en relación con la gravedad de la insuficiencia placentaria.

INTRODUCTION: Intrauterine growth restriction (IUGR) and prematurity have been associated with increased perinatal morbidity and mortality and also with cardiovascular foetal programming. However, there are few studies on the impact of placenta-related IUGR on perinatal outcomes and cardiovascular biomarkers in pre-term infants. OBJECTIVES: To determine differences in neonatal morbidity, mortality and cord blood biomarkers of cardiovascular dysfunction between pre-term placenta-related IUGR and non-IUGR new-borns, and to analyse their relationship with the severity of IUGR according to foetal Doppler evaluation. MATERIAL AND METHODS: Prospective cohort study: pre-term infants with placenta-related IUGR and matched pre-term infants without IUGR. A Doppler scan was performed, and placenta-IUGR was classified according to severity. Comparative analysis of perinatal outcomes, neonatal morbidity and mortality, and cord blood levels of biomarkers of cardiovascular dysfunction was performed. RESULTS: IUGR new-borns present lower weight, length, head circumference, and Apgar score at birth, as well as increased neonatal and cardiovascular dysfunction biomarker levels, compared with pre-term new-borns without IUGR. These differences increase with the severity of IUGR determined by prenatal umbilical artery Doppler scan. CONCLUSIONS: Placenta-related-IUGR pre-term infants, irrespective of gestational age, present increased neonatal morbidity and mortality that is significantly proportional to the severity of IUGR. Placental impairment and severity also determine levels of cardiovascular dysfunction biomarkers at birth.

Neurodevelopment in preterm infants with and without placenta-related intrauterine growth restriction and its relation to perinatal and postnatal factors.

OBJECTIVE: Intrauterine-growth restriction is associated with impaired neurodevelopment. However, studies on early childhood neurodevelopment of premature infants with placenta-related intrauterine-growth restriction (IUGR) are scarce and heterogeneous. We aimed to analyze the impact of placenta-related IUGR on preschool age neurodevelopment in preterm infants, and to ascertain which prenatal and postnatal factors influence neurodevelopment in these infants. METHODS: Prospective cohorts study: 48 placenta-related IUGR premature infants and 25 matched non-IUGR premature infants (mean gestational age: 31.4 and 31.6 weeks, respectively). Preschool neurodevelopment assessment with cognitive Bayley Scales III and with ASQ-III surveys (age interval: 34.07-42.50 months). Inter-cohort result comparison. Analysis of perinatal and environmental factors associated with impaired neurodevelopment in both cohorts. RESULTS: No statistically significant neurodevelopment differences were observed at preschool age between both preterm cohorts. Multivariate analysis of perinatal and environmental factors showed daycare, breastfeeding, higher parental educational level, and absence of severe neonatal morbidity to be associated with a lower risk of altered neurodevelopment at preschool age. CONCLUSIONS: Placenta-related IUGR does not have a significant impact on preschool neurodevelopment in our preterm patients. Instead, post-natal positive environmental factors such as parental educational level, breastfeeding, and daycare attendance make a difference towards an improvement in neurodevelopment in these infants.

Anti-annexin A5 antibodies in women with spontaneous pregnancy loss.

BACKGROUND AND OBJECTIVE: The aim was to evaluate the role of anti-annexin A5 (anti-ANXA5) antibodies as risk factor for recurrent miscarriage (RM) and unexplained fetal loss (UFL). PATIENTS AND METHODS: Retrospective, cohort study. SETTING: Vall d'Hebron University Hospital. SUBJECTS: 122 women, in two groups: STUDY GROUP: 54 women with RM/UFL and control group: 68 pregnant without RM/UFL. INTERVENTION: Antiphospholipid, mainly anti-ANXA5 antibody analysis. Comparison of all antiphospholipid antibodies between groups. RESULTS: Antiphospholipid antibody (aPL) prevalence in the study group was 10/54 (14.8%) and 5/68 (7.3%) in control group (p=0.09). In the RM subgroup, it was 3/25 and 9/34 in UFL versus 5/68 in controls (p=0.013). Lupus anticoagulant (LA) was present in 4 cases, all belonging to the study group (p=0.011). Four out of 34 women with UFL were positive for anticardiolipin antibodies-IgG (IgG-aCL) versus 1/68 in controls (p=0.041). In RM subgroup, anti-ANXA5 antibodies were positive in 2/25 versus 3/68 in controls, and in UFL subgroup, 3/34 versus 3/68 cases (p=1.000). CONCLUSION: According to our results, anti-ANXA5 antibodies should not be considered as a risk factor for RM/UFL.

Are anti-beta-glycoprotein-I antibodies markers for recurrent pregnancy loss in lupus anticoagulant/anticardiolipin seronegative women?

PROBLEM: Anti-beta(2)-Glicoprotein-1 antibodies (anti-beta(2)GPI-ab) have been related to recurrent miscarriage (RM) with conflicting results. The aim was to evaluate the role of anti-beta(2)-GPI-ab as unique biological marker in RM related to antiphospholipid (aPL). METHOD OF STUDY: A cohort study that included 59 cases, divided in two groups, was designed: group 1 comprised 43 pregnant women with 'obstetric' antiphospholipid syndrome (APS) and group 2 included 16 cases with similar complaints but only having repeatedly anti-beta(2)-GPI-ab. Previous thrombosis and/or inherited thrombophilia were excluded. Lupus anticoagulant, anticardiolipin antibodies (aCA), anti-beta(2)-GPI-ab, and other autoantibodies were analyzed. Miscarriages, premature births, pre-eclampsia, live births, placental and systemic thromboses were studied. RESULTS: No differences in previous obstetric complications were detected (P = 1.00-0.164). After the treatment, differences in number of obstetric complications were not seen (P = 1.00). Live births were similar in two groups (88.4% and 93.7%; P = 1.00). Placental thrombosis was equal in both groups, 93.3% versus 80% (P = 1.00). CONCLUSION: These results suggest that anti-beta(2)-GPI-ab may be considered a biological marker for obstetric APS.