Trends for Neonatal Deaths in Nepal (2001–2016) to Project Progress Towards the SDG Target in 2030, and Risk Factor Analyses to Focus Action

Introduction

Nepal has made considerable progress on improving child survival during the Millennium Development Goal period, however, further progress will require accelerated reduction in neonatal mortality. Neonatal survival is one of the priorities for Sustainable Development Goals 2030. This paper examines the trends, equity gaps and factors associated with neonatal mortality between 2001 and 2016 to assess the likelihood of Every Newborn Action Plan (ENAP) target being reached in Nepal by 2030.

Methods

This study used data from the 2001, 2006, 2011 and 2016 Nepal Demographic and Health Surveys. We examined neonatal mortality rate (NMR) across the socioeconomic strata and the annual rate of reduction (ARR) between 2001 and 2016. We assessed association of socio-demographic, maternal, obstetric and neonatal factors associated with neonatal mortality. Based on the ARR among the wealth quintile between 2001 and 2016, we made projection of NMR to achieve the ENAP target. Using the Lorenz curve, we calculated the inequity distribution among the wealth quintiles between 2001 and 2016.

Results

In NDHS of 2001, 2006, 2011 and 2016, a total of 8400, 8600, 13,485 and 13,089 women were interviewed respectively. There were significant disparities between wealth quintiles that widened over the 15 years. The ARR for NMR declined with an average of 4.0% between 2001 and 2016. Multivariate analysis of the 2016 data showed that women who had not been vaccinated against tetanus had the highest risk of neonatal mortality (adjusted odds ratio [AOR] 3.38; 95% confidence interval [CI] 1.20–9.55), followed by women who had no education (AOR 1.87; 95% CI 1.62–2.16). Further factors significantly associated with neonatal mortality were the mother giving birth before the age of 20 (AOR 1.76; CI 95% 1.17–2.59), household air pollution (AOR 1.37; CI 95% 1.59–1.62), belonging to a poorest quintile (AOR 1.37; CI 95% 1.21–1.54), residing in a rural area (AOR 1.28; CI 95% 1.13–1.44), and having no toilet at home (AOR 1.21; CI 95% 1.06–1.40). If the trend of neonatal mortality rate of 2016 continues, it is projected that the poorest family will reach the ENAP target in 2067.

Conclusions

Although neonatal mortality is declining in Nepal, if the current trend continues it will take another 50 years for families in the poorest group to attain the 2030 ENAP target. There are different factors associated with neonatal mortality, reducing the disparities for maternal and neonatal care will reduce mortality among the poorest families.

     

Differential biliary excretion of genistein metabolites following intraduodenal and intravenous infusion of genistin in female rats

The purpose of this study was to determine whether bioflavonoid glucoside O-conjugates are absorbed from the intestine in the intact form or as their aglycones following hydrolysis by intestinal beta-glucosidases. In this study, the intestinal absorption of genistin, the beta-glucoside of the isoflavone genistein, was examined in anesthetized, adult female rats fitted with indwelling biliary cannulas. To first establish whether genistein, once absorbed, was converted into unique metabolites, genistin was infused into the femoral or portal veins and bile samples quantitatively collected. Analysis of bile samples by HPLC-mass spectrometry revealed that almost full recovery of the genistein component occurred in the form of unreacted genistin ( approximately 20%) and genistein 7beta-O-glucuronide ( approximately 80%). However, when genistin was infused into the upper small intestine, only genistein 7beta-O-glucuronide and the aglycone genistein appeared in the bile. There was no evidence for any biliary secretion of the unreacted genistin, thereby excluding its uptake in the intact form from the small intestine in this animal model.     

Tamoxifen inhibits malignant peripheral nerve sheath tumor growth in an estrogen receptor-independent manner

Few therapeutic options are available for malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with neurofibromatosis type 1 (NF1). Guided by clinical observations suggesting that some NF1-associated nerve sheath tumors are hormonally responsive, we hypothesized that the selective estrogen receptor (ER) modulator tamoxifen would inhibit MPNST tumorigenesis in vitro and in vivo. To test this hypothesis, we examined tamoxifen effects on MPNST cell proliferation and survival, MPNST xenograft growth, and the mechanism by which tamoxifen impeded these processes. We found that 1-5 μM 4-hydroxy-tamoxifen induced MPNST cell death, whereas 0.01-0.1 μM 4-hydroxy-tamoxifen inhibited mitogenesis. Dermal and plexiform neurofibromas, MPNSTs, and MPNST cell lines expressed ERβ and G-protein-coupled ER-1 (GPER); MPNSTs also expressed estrogen biosynthetic enzymes. However, MPNST cells did not secrete 17β-estradiol, exogenous 17β-estradiol did not stimulate mitogenesis or rescue 4-hydroxy-tamoxifen effects on MPNST cells, and the steroidal antiestrogen ICI-182,780 did not mimic tamoxifen effects on MPNST cells. Further, ablation of ERβ and GPER had no effect on MPNST proliferation, survival, or tamoxifen sensitivity, indicating that tamoxifen acts via an ER-independent mechanism. Consistent with this hypothesis, inhibitors of calmodulin (trifluoperazine, W-7), another known tamoxifen target, recapitulated 4-hydroxy-tamoxifen effects on MPNST cells. Tamoxifen was also effective in vivo, demonstrating potent antitumor activity in mice orthotopically xenografted with human MPNST cells. We conclude that 4-hydroxy-tamoxifen inhibits MPNST cell proliferation and survival via an ER-independent mechanism. The in vivo effectiveness of tamoxifen provides a rationale for clinical trials in cases of MPNSTs.     

The hr locus and the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in newborn mice

 In mice, the recessive mutation hairless (hr) controls the cutaneous response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) but its influence on TCDD’s systemic toxicity is unclear. To clarify this, we compared the effects of lactational TCDD exposure on standardized litters of newborn HRS/J mice homozygous for either hr or + that were fostered by haired dams exposed to 0, 6, 8 or 12 μg TCDD/kg body weight on postnatal day 0. At 12 μg/kg, TCDD was lethal to both haired and hairless pups. At the lower doses (6 and 8 μg/kg) the survival of hr/hr pups was significantly lower than +/+ pups. Affected pups succumbed following a 1 to 2-day period of cachexia and wasting. As has been reported for other mouse strains, TCDD exposure impacted on their neonatal development and lessened the time to eye opening for both haired and hairless pups. However, the hairless animals were affected at lower doses than were the haired. The results of this study document that the hr/hr genotype does influence the systemic toxicity of TCDD in mice. Received: 26 April 1994 / Accepted: 23 June 1994     

Oesophagus in progressive systemic sclerosis: A clinical,radiological and manometric evaluation

Ten patients with progressive systemic sclerosis underwent clinical, radiological and manometric evaluation for oesophageal dysfunction. Seven had typical dermatological features of this disease. Eight had symptoms of gastroesophageal reflux. Barium oesophagogram showed sluggish or absent peristalsis with delayed emptying of barium in six. Motility disturbances noted on barium oesophagogram were confirmed by oesophageal manometry which proved to be the most sensitive test in diagnosis of progessive systemic sclerosis.     

Adoptive transfer of tolerance induced by ICRC bacilli against Mycobacterium leprae in mice

ICRC bacilli, the cultivable leprosy-derived mycobacteria, isolated from lepromatous nodules of leprosy patients were found to be immunogenic in BALB/c mice at a dose of 2 X 10(7) acid-fast bacilli when injected by the intradermal (i.d.) route. The sensitization to lepromin and ICRC antigens was measured by the foot pad enlargement (FPE) method. The same dose of bacilli when injected by intravenous (i.v.), intraperitoneal, and subcutaneous routes induced immune tolerance in mice as indicated by reduction in the FPE to the test antigens. The spleen cells obtained after i.v. injection of ICRC bacilli/Mycobacterium leprae after adoptive transfer brought about suppression of delayed-type hypersensitivity in sensitized as well as nonsensitized recipients, indicating production of suppressor cells after i.v. injection. Similarly, the tolerance induced by i.v. injection of M. leprae in mice could be partially converted to immunity by i.d. sensitization with live BCG and two strains of ICRC bacilli (C-44 and C-75).