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Abstract Background Compliance with standards of care is required for sustained improvement in the quality of delivery services. It thus represents a key challenge to improving maternal survival and meeting the Sustainable Development Goal (SDG) target of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. This study examines the extent to which normal low-risk health facility deliveries in Nepal meet the standards of quality of care and assesses the effect of the standards of quality of care and various contextual factors on women’s satisfaction with the services they receive. Methods Drawing on the 2021 Nepal Health Facility Survey, the sample comprised 320 women who used health facilities for normal, low-risk delivery services. A weighted one-sample t-test was applied to examine the proportion of deliveries meeting the eight standards of care. Women’s overall satisfaction level was computed from seven satisfaction variables measured on a Likert scale, using principal component analysis. The composite measure was then dichotomized. Binary logistic regression was used to analyze the determinants of women’s satisfaction with delivery care services. Results Deliveries complying with the eight standards of care and its 53 indicators varied widely; output indicators were more frequently met than input indicators. Of the eight standards of care, the “functional referral system” performed highest (92.0%), while “competent, motivated human resources” performed the least (52.4%). Women who were attended by a provider when they called for support (AOR: 5.29; CI: 1.18, 23.64), who delivered in health facilities that displayed health statistics (AOR 3.16; CI: 1.87, 5.33), who experienced caring behaviors from providers (AOR: 2.59; CI: 1.06, 6.30) and who enjoyed audio-visual privacy (AOR 2.13; CI: 1.04, 4.38) had higher satisfaction levels compared to their counterparts. The implementation of the Maternity Incentive Scheme and presence of a maternal waiting room in health facilities, however, were associated with lower satisfaction levels. Conclusions Nepal performed moderately well in meeting the standards of care for normal, low-risk deliveries. To meet the SDG target Nepal must accelerate progress. It needs to focus on people-centered quality improvement to routinely assess the standards of care, mobilize available resources, improve coordination among the three tiers of government, and implement high-impact programs.

Abstract Background Nepal is committed to achieving the Sustainable Development Goal (SDG) 2030 target 3.1 of reducing the maternal mortality ratio to 70 deaths per 100,000 live births. Along with increasing access to health facility (HF)-based delivery services, improving HF readiness is critically important. The majority of births in Nepal are normal low-risk births and most of them take place in public HFs, as does the majority of maternal deaths. This study aims to assess changes in HF readiness in Nepal between 2015 and 2021, notably, if HF readiness for providing high-quality services for normal low-risk deliveries improved; if the functionality of basic emergency obstetric and neonatal care (BEmONC) services increased; and if infection prevention and control improved. Methods Cross-sectional data from two nationally representative HF-based surveys in 2015 and 2021 were analyzed. This included 457 HFs in 2015 and 804 HFs in 2021, providing normal low-risk delivery services. Indices for HF readiness for normal low-risk delivery services, BEmONC service functionality, and infection prevention and control were computed. Independent sample T-test was used to measure changes over time. The results were stratified by public versus private HFs. Results Despite a statistically significant increase in the overall HF readiness index for normal low-risk delivery services, from 37.9% in 2015 to 43.7%, in 2021, HF readiness in 2021 remained inadequate. The availability of trained providers, essential medicines for mothers, and basic equipment and supplies was high, while that of essential medicines for newborns was moderate; availability of delivery care guidelines was low. BEmONC service functionality did not improve and remained below five percent facility coverage at both time points. In private HFs, readiness for good quality obstetrical care was higher than in public HFs at both time points. The infection prevention and control index improved over time; however, facility coverage in 2021 remained below ten percent. Conclusions The slow progress and sub-optimal readiness for normal, low-risk deliveries and infection prevention and control, along with declining and low BEmONC service functionality in 2021 is reflective of poor quality of care and provides some proximate explanation for the moderately high maternal mortality and the stagnation of neonatal mortality in Nepal. To reach the SDG 2030 target of reducing maternal deaths, Nepal must hasten its efforts to strengthen supply chain systems to enhance the availability and utilization of essential medicines, equipment, and supplies, along with guidelines, to bolster the human resource capacity, and to implement mechanisms to monitor quality of care. In general, the capacity of local governments to deliver basic healthcare services needs to be increased.

Abstract Background Endometrial carcinomas are the most common female genital malignancies. They are very rare in pregnancy and worldwide less than 60 cases associated with pregnancy are published. No clear cell carcinoma has been described in a pregnancy with a live birth. Case presentation We present the course of a 43-year-old Uyghur female patient with the diagnosis of endometrial carcinoma with a deficiency in the DNA mismatch repair system in the pregnancy. The malignancy with clear cell histology was confirmed by biopsy following the delivery via caesarean section due to preterm birth of a fetus with sonographically suspected tetralogy of Fallot. Earlier whole exome sequencing after amniocentesis had shown a heterozygous mutation in the MSH2 gene, which was unlikely to be related to the fetal cardiac defect. The uterine mass was initially deemed an isthmocervical fibroid by ultrasound and was confirmed as stage II endometrial carcinoma. The patient was consequently treated with surgery, radiotherapy and chemotherapy. Six months after the adjuvant therapy, re-laparotomy was performed due to ileus symptoms and an ileum metastasis was found. The patient is currently undergoing immune checkpoint inhibitor therapy with pembrolizumab. Conclusion Rare endometrial carcinoma should be included in the differential diagnosis of uterine masses in pregnant women with risk factors.

Abstract Background Obesity in pregnancy and related early-life factors place the offspring at the highest risk of being overweight. Despite convincing evidence on these associations, there is an unmet public health need to identify “high-risk” offspring by predicting very early deviations in weight gain patterns as a subclinical stage towards overweight. However, data and methods for individual risk prediction are lacking. We aimed to identify those infants exposed to obesity in pregnancy at ages 3 months, 1 year, and 2 years who likely will follow a higher-than-normal body mass index (BMI) growth trajectory towards manifest overweight by developing an early-risk quantification system. Methods This study uses data from the prospective mother-child cohort study Programming of Enhanced Adiposity Risk in CHildhood–Early Screening (PEACHES) comprising 1671 mothers with pre-conception obesity and without (controls) and their offspring. Exposures were pre- and postnatal risks documented in patient-held maternal and child health records. The main outcome was a “higher-than-normal BMI growth pattern” preceding overweight, defined as BMI z-score >1 SD (i.e., World Health Organization [WHO] cut-off “at risk of overweight”) at least twice during consecutive offspring growth periods between age 6 months and 5 years. The independent cohort PErinatal Prevention of Obesity (PEPO) comprising 11,730 mother-child pairs recruited close to school entry (around age 6 years) was available for data validation. Cluster analysis and sequential prediction modelling were performed. Results Data of 1557 PEACHES mother-child pairs and the validation cohort were analyzed comprising more than 50,000 offspring BMI measurements. More than 1-in-5 offspring exposed to obesity in pregnancy belonged to an upper BMI z-score cluster as a distinct pattern of BMI development (above the cut-off of 1 SD) from the first months of life onwards resulting in preschool overweight/obesity (age 5 years: odds ratio [OR] 16.13; 95% confidence interval [CI] 9.98–26.05). Contributing early-life factors including excessive weight gain (OR 2.08; 95% CI 1.25–3.45) and smoking (OR 1.94; 95% CI 1.27–2.95) in pregnancy were instrumental in predicting a “higher-than-normal BMI growth pattern” at age 3 months and re-evaluating the risk at ages 1 year and 2 years (area under the receiver operating characteristic [AUROC] 0.69–0.79, sensitivity 70.7–76.0%, specificity 64.7–78.1%). External validation of prediction models demonstrated adequate predictive performances. Conclusions We devised a novel sequential strategy of individual prediction and re-evaluation of a higher-than-normal weight gain in “high-risk” infants well before developing overweight to guide decision-making. The strategy holds promise to elaborate interventions in an early preventive manner for integration in systems of well-child care.

Abstract Background Disparities in the use of maternal, neonatal and child health (MNCH) services remain a concern in Low- and Middle-Income countries such as Nepal. Commonly observed disparities exist in education, income, ethnic groups, administrative regions and province-level in Nepal. In order to improve equitable outcomes for MNCH and to scale-up quality services, an Investment Case (IC) approach was lunched in the Asia Pacific region. The study assessed the impact of the IC intervention package in maternal and child health outcomes in Nepal. Methods The study used a quasi-experimental design extracting data from the Nepal Demographic Health Surveys – 2011 (pre-assessment) and 2016 (post-assessment) for 16 intervention and 24 control districts. A Difference in Difference (DiD) analysis was conducted to assess the impact of the intervention on maternal and child health outcomes. The linear regression method was used to calculate the DiD, adjusting for potential covariates. The final models were arrived by stepwise backward method including the confounding variables significant at p

BackgroundInvestment Case is a participatory approach that has been used over the years for better strategic actions and planning in the health sector. Based on this approach, a District Investment Case (DIC) program was launched to improve maternal, neonatal and child health services in partnership with government, non-government sectors and UNICEF Nepal. In the meantime, this study aimed to explore perceptions and experiences of local stakeholders regarding health planning and budgeting and explore the role of the DIC program in ensuring equity in access to maternal and child health services.MethodsThis study adopted an exploratory phenomenography design with a purposive sampling technique for data collection. Three DIC implemented districts and three comparison districts were selected and total 30 key informant interviews with district level stakeholders and six focus groups with community stakeholders were carried out. A deductive approach was used to explore the perception of local stakeholders of health planning and budgeting of the health care expenses on the local level.ResultsInvestment Case approach helped stakeholders in planning systematically based on evidence through collaborative and participatory approach while in comparison areas previous year plan was mainly primarily considered as reference. Resource constraints and geographical difficulty were key barriers in executing the desired plan in both intervention and comparison districts. Positive changes were observed in coverage of maternal and child health services in both groups. A few participants reported no difference due to the DIC program. The participants specified the improvement in access to information, access and utilization of health services by women. This has influenced the positive health care seeking behavior.ConclusionsThe decentralized planning and management approach at the district level helps to ensure equity in access to maternal, newborn and child health care. However, quality evidence, inclusiveness, functional feedback and support system and local resource utilization should be the key consideration.

Abstract Background Intestinal parasitic infections (IPI) lead to significant morbidity and mortality in pediatric and adult populations worldwide. Intestinal parasitism during pregnancy is of interest as it may affect the health of pregnant women and their offspring. This study determined the prevalence of IPI in pregnant women living in substandard conditions in three urban districts of Bogotá, Colombia. Associations between prevalence and sociodemographic factors, housing, and living conditions were also evaluated. Methods In a cross-sectional and community-based study, pregnant women were recruited from three districts of Bogotá. A total of 550 participants answered a questionnaire; 331 of these also provided stool samples, with 233 providing one and 98 providing two stool samples. Questionnaire responses were associated with the presence of intestinal parasites, which was determined using a standard combined microscopy technique including direct wet mount and formol–ether concentration. Results were verified by supplementary examination of 48 stool samples by quantitative polymerase chain reaction (qPCR). Results Among pregnant women who lived in selected poor residential areas in Bogotá, the overall prevalence of intestinal parasitism was 41% with 9% polyparasitism. Pathogenic parasites were present in 1.2% of the 331 participants including Giardia lamblia and Ascaris lumbricoides. Higher prevalence was found for parasites with debated pathogenicity, including Blastocystis hominis (25%), Endolimax nana (15%), Entamoeba coli (8%), and Iodamoeba butschlii (2%). Entamoeba histolytica/dispar complex was also detected (1.5%). When comparing a subset of stool samples using the combined microscopy technique and qPCR, the latter detected a higher 58.3% overall IPI prevalence. Higher prevalence of infections by any intestinal parasite was found in participants who had never been dewormed (p = 0.01). Higher but not statistically significant associations were found between any parasite and women living with a partner, and intestinal polyparasitism and being from a minority group and not having a water sink. Conclusions This first study of the prevalence of intestinal parasitism in Bogotá focused on pregnant women living in poverty, found a high prevalence of intestinal parasites of debated pathogenicity, and confirmed a low prevalence of pathogenic intestinal parasites. These results highlight the need for educational interventions to disrupt transmission routes for prevalent parasites.

Abstract Background Giving birth assisted by skilled care in a health facility plays a vital role in preventing maternal deaths. In Nepal, delivery services are free and a cash incentive is provided to women giving birth at a health facility. Nevertheless, about half of women still deliver at home. This study explores socio-cultural and health service-related barriers to and facilitators of institutional delivery. Methods Six village development committees in hill and plain areas were selected in Chitwan district. We conducted a total of 10 focus group discussions and 12 in-depth-interviews with relevant stakeholder groups, including mothers, husbands, mothers-in-law, traditional birth attendants, female community health volunteers, health service providers and district health managers. Data were analyzed inductively using thematic analysis. Results Three main themes played a role in deciding the place of delivery, i.e. socio-cultural norms and values; access to birthing facilities; and perceptions regarding the quality of health services. Factors encouraging an institutional delivery included complications during labour, supportive husbands and mothers-in-law, the availability of an ambulance, having birthing centres nearby, locally sufficient financial incentives and/or material incentives, the 24-h availability of midwives and friendly health service providers. Socio-cultural barriers to institutional deliveries were deeply held beliefs about childbirth being a normal life event, the wish to be cared for by family members, greater freedom of movement at home, a warm environment, the possibility to obtain appropriate “hot” foods, and shyness of young women and their position in the family hierarchy. Accessibility and quality of health services also presented barriers, including lack of road and transportation, insufficient financial incentives, poor infrastructure and equipment at birthing centres and the young age and perceived incompetence of midwives. Conclusion Despite much progress in recent years, this study revealed some important barriers to the utilization of health services. It suggests that a combination of upgrading birthing centres and strengthening the competencies of health personnel while embracing and addressing deeply rooted family values and traditions can improve existing programmes and further increase institutional delivery rates.

Primary Epstein-Barr-Virus (EBV)-associated pulmonary lymphoepithelioma-like carcinoma (LELC) is an aggressive rare cancer. Higher incidences have been observed in Asian sub-populations. Multimodal treatment paradigms have emerged as promising novel strategies in the management of advanced NSCLC. In this report, we describe the case of a 34-year-old female patient of Asian origin with a post-partum initial diagnosis of pulmonary LELC. Multimodal treatment with chemoimmunotherapy and hypofractionated irradiation to the primary tumour and main metastatic sites led to a favourable response demonstrating that radiotherapy may potentially augment anti-tumour immunity. To the best of our knowledge, this is the first case report on this novel therapy strategy of multi-site hypofractionated radiotherapy and chemoimmunotherapy for metastatic pulmonary EBV-associated LELC.

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality and morbidity. The WOMAN trial showed that tranexamic acid (TXA) reduces death due to bleeding in women with PPH. To determine whether TXA has pro-thrombotic effects in women with PPH, we measured endogenous thrombin potential (ETP), coagulation factors V, VIII, von Willebrand (vW), fibrinogen, D-Dimers and platelet function. Methods: We conducted a sub-study within the WOMAN trial, an international randomized, parallel-group, double blind, placebo-controlled trial. Women with primary PPH were randomly allocated to receive 1 gram of tranexamic acid or matching placebo. Baseline blood samples were collected just prior to the first dose and a follow up sample was collected 30±15 minutes afterwards. We compared before and after changes in coagulation parameters between treatment groups using repeated measurement ANOVA. Change in ETP was the primary outcome. We did an intention-to-treat analysis using ANCOVA with adjustment for baseline and the time interval between the blood samples. Findings: A total of 187 patients were randomized to receive TXA (n=93) or matching placebo (n=94). Six patients were excluded due to incomplete data. The reduction in ETP from baseline to follow up was 43.2 nM*min (95%CI, -16.6 to 103.1) in the TXA group and 4.6 nM*min (95%CI, -51.4 to 60.6) in the placebo group. The difference was not statistically significant (95%CI, -42.9 to 120). There were no significant effects of TXA treatment on any other parameters (ADPtest, TRAPtest, coagulation factors activity, fibrinogen levels, D-Dimer level). Conclusion: We found no evidence that tranexamic acid treatment for PPH has substantial pro-coagulant effects. However, larger studies are needed to confirm or refute more modest effects. Trial registration: ISRCTN76912190 (initially registered 10/12/2008, WOMAN-ETAPlat included on 28/10/2013) and NCT00872469 (initially registered 31/03/2009, WOMAN-ETAPlat included on 28/10/2013).

BACKGROUND:Maternal pre-conception obesity is a strong risk factor for childhood overweight. However, prenatal mechanisms and their effects in susceptible gestational periods that contribute to this risk are not well understood. We aimed to assess the impact of late-pregnancy dysglycemia in obese pregnancies with negative testing for gestational diabetes mellitus (GDM) on long-term mother-child outcomes. METHODS AND FINDINGS:The prospective cohort study Programming of Enhanced Adiposity Risk in Childhood-Early Screening (PEACHES) (n = 1,671) enrolled obese and normal weight mothers from August 2010 to December 2015 with trimester-specific data on glucose metabolism including GDM status at the end of the second trimester and maternal glycated hemoglobin (HbA1c) at delivery as a marker for late-pregnancy dysglycemia (HbA1c ≥ 5.7% [39 mmol/mol]). We assessed offspring short- and long-term outcomes up to 4 years, and maternal glucose metabolism 3.5 years postpartum. Multivariable linear and log-binomial regression with effects presented as mean increments (Δ) or relative risks (RRs) with 95% confidence intervals (CIs) were used to examine the association between late-pregnancy dysglycemia and outcomes. Linear mixed-effects models were used to study the longitudinal development of offspring body mass index (BMI) z-scores. The contribution of late-pregnancy dysglycemia to the association between maternal pre-conception obesity and offspring BMI was estimated using mediation analysis. In all, 898 mother-child pairs were included in this unplanned interim analysis. Among obese mothers with negative testing for GDM (n = 448), those with late-pregnancy dysglycemia (n = 135, 30.1%) had higher proportions of excessive total gestational weight gain (GWG), excessive third-trimester GWG, and offspring with large-for-gestational-age birth weight than those without. Besides higher birth weight (Δ 192 g, 95% CI 100-284) and cord-blood C-peptide concentration (Δ 0.10 ng/ml, 95% CI 0.02-0.17), offspring of these women had greater weight gain during early childhood (Δ BMI z-score per year 0.18, 95% CI 0.06-0.30, n = 262) and higher BMI z-score at 4 years (Δ 0.58, 95% CI 0.18-0.99, n = 43) than offspring of the obese, GDM-negative mothers with normal HbA1c values at delivery. Late-pregnancy dysglycemia in GDM-negative mothers accounted for about one-quarter of the association of maternal obesity with offspring BMI at age 4 years (n = 151). In contrast, childhood BMI z-scores were not affected by a diagnosis of GDM in obese pregnancies (GDM-positive: 0.58, 95% CI 0.36-0.79, versus GDM-negative: 0.62, 95% CI 0.44-0.79). One mechanism triggering late-pregnancy dysglycemia in obese, GDM-negative mothers was related to excessive third-trimester weight gain (RR 1.72, 95% CI 1.12-2.65). Furthermore, in the maternal population, we found a 4-fold (RR 4.01, 95% CI 1.97-8.17) increased risk of future prediabetes or diabetes if obese, GDM-negative women had a high versus normal HbA1c at delivery (absolute risk: 43.2% versus 10.5%). There is a potential for misclassification bias as the predominantly used GDM test procedure changed over the enrollment period. Further studies are required to validate the findings and elucidate the possible third-trimester factors contributing to future mother-child health status. CONCLUSIONS:Findings from this interim analysis suggest that offspring of obese mothers treated because of a diagnosis of GDM appeared to have a better BMI outcome in childhood than those of obese mothers who-following negative GDM testing-remained untreated in the last trimester and developed dysglycemia. Late-pregnancy dysglycemia related to uncontrolled weight gain may contribute to the development of child overweight and maternal diabetes. Our data suggest that negative GDM testing in obese pregnancies is not an "all-clear signal" and should not lead to reduced attention and risk awareness of physicians and obese women. Effective strategies are needed to maintain third-trimester glycemic and weight gain control among otherwise healthy obese pregnant women.

Background. Postpartum haemorrhage (PPH) is a potentially life-threatening complication for women, and the leading cause of maternal mortality. Tranexamic acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and to reduce blood loss in general surgery. TXA may have effects on thrombin generation, platelet function and coagulation factors as a result of its inhibition on the plasmin. Methods. WOMAN ETAPlaT is a sub-study of the World Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically diagnosed with PPH after a vaginal delivery or caesarean section, are eligible for inclusion in the study. Blood samples will be collected at the baseline and 30 minutes after the first dose of study treatment is given. Platelet function will be evaluated in whole blood immediately after sampling with Multiplate® tests (ADPtest and TRAPtest). Thrombin generation, fibrinogen, D-dimer, and coagulation factors vW, V and VIII will be analysed using platelet poor plasma. Results. Recruitment to WOMAN ETAPlaT started on 04 November 2013 and closed on 13 January 2015, during this time 188 patients were recruited. The final participant follow-up was completed on 04 March 2015. This article introduces the statistical analysis plan for the study, without reference to unblinded data. Conclusion. The data from this study will provide evidence for the effect of TXA on thrombin generation, platelet function and coagulation factors in women with PPH. Trial registration: ClinicalTrials.gov Identifier: NCT00872469; ISRCTN76912190

Background. Postpartum haemorrhage (PPH) is a potentially life-threatening complication for women, and the leading cause of maternal mortality. Tranexamic acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and to reduce blood loss in general surgery. TXA may have effects on thrombin generation, platelet function and coagulation factors as a result of its inhibition on the plasmin. Methods. WOMAN ETAPlaT is a sub-study of the World Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically diagnosed with PPH after a vaginal delivery or caesarean section, are eligible for inclusion in the study. Blood samples will be collected at the baseline and 30 minutes after the first dose of study treatment is given. Platelet function will be evaluated in whole blood immediately after sampling with Multiplate® tests (ADPtest and TRAPtest). Thrombin generation, fibrinogen, D-dimer, and coagulation factors vW, V and VIII will be analysed using platelet poor plasma. Results. Recruitment to WOMAN ETAPlaT started on 04 November 2013 and closed on 13 January 2015, during this time 188 patients were recruited. The final participant follow-up was completed on 04 March 2015. This article introduces the statistical analysis plan for the study, without reference to unblinded data. Conclusion. The data from this study will provide evidence for the effect of TXA on thrombin generation, platelet function and coagulation factors in women with PPH. Trial registration: ClinicalTrials.gov Identifier: NCT00872469; ISRCTN76912190