Increased immunization coverage addresses the equity gap in Nepal.

OBJECTIVE: To compare immunization coverage and equity distribution of coverage between 2001 and 2014 in Nepal. METHODS: We used data from the Demographic and Health Surveys carried out in 2001, 2006 and 2011 together with data from the 2014 Multiple Indicator Cluster Survey. We calculated the proportion, in mean percentage, of children who had received bacille Calmette-Guérin (BCG) vaccine, three doses of polio vaccine, three doses of diphtheria-pertussis-tetanus (DPT) vaccine and measles vaccine. To measure inequities between wealth quintiles, we calculated the slope index of inequality (SII) and relative index of inequality (RII) for all surveys. FINDINGS: From 2001 to 2014, the proportion of children who received all vaccines at the age of 12 months increased from 68.8% (95% confidence interval, CI: 67.5-70.1) to 82.4% (95% CI: 80.7-84.0). While coverage of BCG, DPT and measles immunization statistically increased during the study period, the proportion of children who received the third dose of polio vaccine decreased from 93.3% (95% CI: 92.7-93.9) to 88.1% (95% CI: 86.8-89.3). The poorest wealth quintile showed the greatest improvement in immunization coverage, from 58% to 77.9%, while the wealthiest quintile only improved from 84.8% to 86.0%. The SII for children who received all vaccines improved from 0.070 (95% CI: 0.061-0.078) to 0.026 (95% CI: 0.013-0.039) and RII improved from 1.13 to 1.03. CONCLUSION: The improvement in immunization coverage between 2001 and 2014 in Nepal can mainly be attributed to the interventions targeting the disadvantaged populations.

Evaluation of Helping Babies Breathe Quality Improvement Cycle (HBB-QIC) on retention of neonatal resuscitation skills six months after training in Nepal.

BACKGROUND: Each year 700,000 infants die due to intrapartum-related complications. Implementation of Helping Babies Breathe (HBB)-a simplified neonatal resuscitation protocol in low-resource clinical settings has shown to reduce intrapartum stillbirths and first-day neonatal mortality. However, there is a lack of evidence on the effect of different HBB implementation strategies to improve and sustain the clinical competency of health workers on bag-and-mask ventilation. This study was conducted to evaluate the impact of multi-faceted implementation strategy for HBB, as a quality improvement cycle (HBB-QIC), on the retention of neonatal resuscitation skills in a tertiary hospital of Nepal. METHODS: A time-series design was applied. The multi-faceted intervention for HBB-QIC included training, daily bag-and-mask skill checks, preparation for resuscitation before every birth, self-evaluation and peer review on neonatal resuscitation skills, and weekly review meetings. Knowledge and skills were assessed through questionnaires, skill checklists, and Objective Structured Clinical Examinations (OSCE) before implementation of the HBB-QIC, immediately after HBB training, and again at 6 months. Means were compared using paired t-tests, and associations between skill retention and HBB-QIC components were analyzed using logistic regression analysis. RESULTS: One hundred thirty seven health workers were enrolled in the study. Knowledge scores were higher immediately following the HBB training, 16.4 ± 1.4 compared to 12.8 ± 1.6 before (out of 17), and the knowledge was retained 6 months after the training (16.5 ± 1.1). Bag-and-mask skills improved immediately after the training and were retained 6 months after the training. The retention of bag-and-mask skills was associated with daily bag-and-mask skill checks, preparation for resuscitation before every birth, use of a self-evaluation checklist, and attendance at weekly review meetings. The implementation strategies with the highest association to skill retention were daily bag-and-mask skill checks (RR-5.1, 95% CI 1.9-13.5) and use of self-evaluation checklists after every delivery (RR-3.8, 95% CI 1.4-9.7). CONCLUSIONS: Health workers who practiced bag-and-mask skills, prepared for resuscitation before every birth, used self-evaluation checklists, and attended weekly review meetings were more likely to retain their neonatal resuscitation skills. Further studies are required to evaluate HBB-QIC in primary care settings, where the number of deliveries is gradually increasing. TRIAL REGISTRATION: ISRCTN97846009 . Date of Registration- 15 August 2012.

Risk factors for antepartum stillbirth: a case-control study in Nepal.

BACKGROUND: Globally, at least 2.65 million stillbirths occur every year, of which more than half are during the antepartum period. The proportion of intrapartum stillbirths has substantially declined with improved obstetric care; however, the number of antepartum stillbirths has not decreased as greatly. Attempts to lower this number may be hampered by an incomplete understanding of the risk factors leading to the majority of antepartum stillbirths. We conducted this study in a tertiary hospital in Nepal to identify the specific risk factors that are associated with antepartum stillbirth in this setting. METHODS: This case-control study was conducted between July 2012 and September 2013. All women who had antepartum stillbirths during this period were included as cases, while 20 % of all women delivering at the hospital were randomly selected and included as referents. Information on potential risk factors was taken from medical records and interviews with the women. Logistic regression analysis was completed to determine the association between those risk factors and antepartum stillbirth. RESULTS: During the study period, 4567 women who delivered at the hospital were enrolled as referents, of which 62 had antepartum stillbirths and were re-categorized into the case population. In total, there were 307 antepartum stillbirths. An association was found between the following risk factors and antepartum stillbirth: increasing maternal age (aOR 1.0, 95 % CI 1.0-1.1), less than five years of maternal education (aOR 2.4, 95 % CI 1.7-3.2), increasing parity (aOR 1.2, 95 % CI 1.0-1.3), previous stillbirth (aOR 2.6, 95 % CI 1.6-4.4), no antenatal care attendance (aOR 4.2, 95 % CI 3.2-5.4), belonging to the poorest family (aOR 1.3, 95 % CI 1.0-1.8), antepartum hemorrhage (aOR 3.7, 95 % CI 2.4-5.7), maternal hypertensive disorder during pregnancy (aOR 2.1, 95 % CI 1.5-3.1), and small weight-for-gestational age babies (aOR 1.5, 95 % CI 1.2-2.0). CONCLUSION: Lack of antenatal care attendance, which had the strongest association with antepartum stillbirth, is a potentially modifiable risk factor, in that increasing the access to and availability of these services can be targeted. Antenatal care attendance provides an opportunity to screen for other potential risk factors for antepartum stillbirth, as well as to provide counseling to women, and thus, helps to ensure a successful pregnancy outcome. CLINICAL TRIAL REGISTRATION: ISRCTN97846009 (url. www.isrctn.com/ISRCTN97846009 ).

Level of mortality risk for babies born preterm or with a small weight for gestation in a tertiary hospital of Nepal.

BACKGROUND: Globally, 15 million babies were born prematurely in 2012, with 37.6 % of them in South Asia. About 32.4 million infants were born small for gestational age (SGA) in 2010, with more than half of these births occurring in South Asia. In Nepal, 14 % of babies were born preterm and 39.3 % were born SGA in 2010. We conducted a study in a tertiary hospital of Nepal to assess the level of risk for neonatal mortality among babies who were born prematurely and/or SGA. METHODS: This case-control study was completed over a 15-month period between July 2012 and September 2013. All neonatal deaths that occurred during the study period were included as cases and 20 % of women with live births were randomly selected as referents. Information on potential risk factors was taken from medical records and interviews with the women. Logistic regression analyses were conducted to determine the level of risk for neonatal mortality among babies born preterm and/or SGA. RESULTS: During this period, the hospital had an incidence of preterm birth and SGA of 8.1 and 37.5%, respectively. In the multivariate model, there was a 12-fold increased risk of neonatal death among preterm infants compared to term. Babies who were SGA had a 40 % higher risk of neonatal death compared to those who were not. Additionally, babies who were both preterm and SGA were 16 times more likely to die during the neonatal period. CONCLUSIONS: Our study showed that the risk of neonatal mortality was highest when the baby was born both preterm and SGA, followed by babies who were born preterm, and then by babies who were SGA in a tertiary hospital in Nepal. In tertiary care settings, the risk of mortality for babies who are born preterm and/or SGA can be reduced with low-cost interventions such as Kangaroo Mother Care or improved management of complications through special newborn care or neonatal intensive care units. The risk of death for babies who are born prematurely and/or SGA can thus be used as an indicator to monitor the quality of care for these babies in health facility settings. CLINICAL TRIAL REGISTRATION: ISRCTN97846009.

Validation of the foot length measure as an alternative tool to identify low birth weight and preterm babies in a low-resource setting like Nepal: a cross-sectional study.

BACKGROUND: The majority of infants who die in the neonatal period are born with a low birth weight (LBW, <2500 grams), or prematurely (before 37 weeks). Most deaths among these infants could be prevented with simple, low-cost interventions like kangaroo mother care (KMC) or prevention and early identification of infection. It is difficult, however, to determine birth weight and gestational age in community settings, and therefore necessary to find an appropriate alternative screening tool that can identify LBW and preterm infants. METHODS: This cross-sectional study was conducted at a tertiary hospital in Nepal to compare the validity of using three different foot length measurement methods (plastic ruler, measuring tape, and paper footprint) as screening tools for identifying babies with birth weights <2000 grams or infants born preterm (<37 weeks). LBW was defined as less than 2000 grams because of the implication for use of KMC for these infants. Non-parametric receiver operating characteristics (ROC) analysis was completed to determine which measurement method best predicted LBW and preterm birth. For the method that was the best predictor for each outcome (i.e. highest area under the curve), further analyses were completed to determine sensitivity, specificity, likelihood ratios and predictive values of an operational screening cutoff to predict LBW or preterm birth in this setting. RESULTS: Of the 811 infants included in this study, 30 infants had LBW and 54 were born preterm. The plastic ruler was the measurement method with the highest area under the curve, and thus predictive score for estimating both outcomes, so operational cutoffs were identified based on this method. An operational cutoff of 7.2 cm was identified to screen for infants weighing <2000 grams at birth (sensitivity: 75.9%, specificity: 90.3%), and 7.8 cm was determined as the operational cutoff to identify preterm infants (sensitivity: 76.9%, specificity: 53.9%). CONCLUSIONS: In Nepal, at least in community settings, foot length measurement with a hard ruler may be a valid proxy to identify at-risk infants when birth weight or gestational age is unavailable. Further studies and piloting should be conducted to identify exact cutoffs that can be used within community settings.

Thioredoxin-1 mediates hypoxia-induced pulmonary artery smooth muscle cell proliferation.

Pathological pulmonary artery smooth muscle cell (PASMC) proliferation contributes to pulmonary vascular remodeling in pulmonary hypertensive diseases associated with hypoxia. Both the hypoxia-inducible factor (HIF) and phosphatidylinositol 3-kinase (PI3K)/serine/threonine kinase (Akt) pathways have been implicated in hypoxia-induced PASMC proliferation. Thioredoxin-1 (Trx1) is a ubiquitously expressed protein that is involved in redox-dependent signaling via HIF and PI3K-Akt in cancer. The role of Trx1 in PASMC proliferation has not been elucidated. The present studies tested the hypothesis that Trx1 regulates hypoxia-induced PASMC proliferation via HIF and/or PI3K- and Akt-dependent mechanisms. Following exposure to chronic hypoxia, our data indicate that Trx1 activity is increased in adult murine lungs. Furthermore, hypoxia-induced increases in cellular proliferation are correlated with increased Trx1 expression, HIF activation, and Akt activation in cultured human PASMC. Both small-interfering RNA-mediated knockdown and pharmacological Trx1 inhibition attenuated hypoxia-induced PASMC proliferation, HIF activation, and Akt activation. While Trx1 knockdown suppressed hypoxia-induced PI3K-Akt activation in PASMC, PI3K-Akt inhibition prevented hypoxia-induced proliferation but had no effect on hypoxia-induced increases in Trx1 or HIF activation. Thus, our findings indicate that Trx1 contributes to hypoxia-induced PASMC proliferation by modulating HIF activation and subsequent PI3K-Akt activation. These novel data suggest that Trx1 might represent a novel therapeutic target to prevent hypoxic PASMC proliferation.

Factors associated with timing of umbilical cord clamping in tertiary hospital of Nepal.

OBJECTIVE: Delayed umbilical cord clamping (DCC) (≥ 60 s) is recognized to improve iron status and neurodevelopment compared to early umbilical cord clamping. The aim of this study is to identify current umbilical cord clamping practice and factors determining the timing of clamping in a low-resource setting where prevalence of anemia in infants is high. RESULTS: A cross-sectional study design including 128 observations of clinical practice in a tertiary-level maternity hospital in Kathmandu, Nepal. Overall 48% of infants received DCC. The mean and median cord clamping times were 61 ± 33 and 57 (38-79) s, respectively. Univariate analysis showed that infants born during the night shift were five times more likely to receive DCC (OR 5.6, 95% CI 1.4-38.0). Additionally, infants born after an obstetric complication were 2.5 times more likely to receive DCC (OR 2.5, 95% CI 1.2-5.3), and babies requiring ventilation had a 65% lower likelihood of receiving DCC (OR 0.35, 95% CI 0.13-0.88). Despite the existence of standard protocols for cord clamping and its proven benefit, the lack of uniformity in the timing of cord clamping reveals poor translation of clinical guidelines into clinical practice. Clinical trial registration ISRCTN97846009.