Summary Progress in newborn survival has been slow, and even more so for reductions in stillbirths. To meet Every Newborn targets of ten or fewer neonatal deaths and ten or fewer stillbirths per 1000 ...births in every country by 2035 will necessitate accelerated scale-up of the most effective care targeting major causes of newborn deaths. We have systematically reviewed interventions across the continuum of care and various delivery platforms, and then modelled the effect and cost of scale-up in the 75 high-burden Countdown countries. Closure of the quality gap through the provision of effective care for all women and newborn babies delivering in facilities could prevent an estimated 113 000 maternal deaths, 531 000 stillbirths, and 1·325 million neonatal deaths annually by 2020 at an estimated running cost of US$4·5 billion per year (US$0·9 per person). Increased coverage and quality of preconception, antenatal, intrapartum, and postnatal interventions by 2025 could avert 71% of neonatal deaths (1·9 million range 1·6–2·1 million), 33% of stillbirths (0·82 million 0·60–0·93 million), and 54% of maternal deaths (0·16 million 0·14–0·17 million) per year. These reductions can be achieved at an annual incremental running cost of US$5·65 billion (US$1·15 per person), which amounts to US$1928 for each life saved, including stillbirths, neonatal, and maternal deaths. Most (82%) of this effect is attributable to facility-based care which, although more expensive than community-based strategies, improves the likelihood of survival. Most of the running costs are also for facility-based care (US$3·66 billion or 64%), even without the cost of new hospitals and country-specific capital inputs being factored in. The maximum effect on neonatal deaths is through interventions delivered during labour and birth, including for obstetric complications (41%), followed by care of small and ill newborn babies (30%). To meet the unmet need for family planning with modern contraceptives would be synergistic, and would contribute to around a halving of births and therefore deaths. Our analysis also indicates that available interventions can reduce the three most common cause of neonatal mortality—preterm, intrapartum, and infection-related deaths—by 58%, 79%, and 84%, respectively.
Neonatal sepsis, a systemic infection in the first 28 days of life, encompasses bloodstream infections, meningitis, and pneumonia. It is the third most common cause of deaths among neonates, ...accounting for 225 000 deaths globally every year.1 South Asia and sub-Saharan Africa have the highest burden of neonatal sepsis in the world. Of the total sepsis related neonatal deaths in 2013, 38.9% occurred in South Asia.12 Poverty, low coverage of effective interventions, including facility births, and gross inequities in delivery of healthcare3 contribute to this situation. We review the available literature (box 1) to draw attention to the burden of neonatal sepsis, the pathogen profile, and the extent of antimicrobial resistance in South Asia, and propose priority actions for policymakers and health professionals in the region.
There is a paucity of data on the epidemiology of sepsis in outborn neonates being referred to level-3 units in low- and middle-income countries (LMIC). The objective of the present study was to ...evaluate the prevalence of sepsis and outcomes of outborn neonates with sepsis, and to characterize the pathogen profile and antimicrobial resistance (AMR) patterns of common isolates in them.
In this prospective observational cohort study (2011-2015), a dedicated research team enrolled all neonates admitted to an outborn level-3 neonatal unit and followed them until discharge/death. Sepsis work-up including blood culture(s) was performed upon suspicion of sepsis. All the isolates were identified and tested for antimicrobial susceptibility. Gram-negative pathogens resistant to any three of the five antibiotic classes (extended-spectrum cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and piperacillin-tazobactam) were labeled multi-drug resistant.
Of the total of 2588 neonates enrolled, culture positive sepsis and total sepsis-i.e. culture positive and/or culture negative sepsis-was diagnosed in 13.1% (95% CI 11.8% to 14.5%) and 54.7% (95% CI 52.8% to 56.6%), respectively. The case fatality rates were 23.4% and 11.0% in culture-positive and total sepsis, respectively. Sepsis accounted for two-thirds of total neonatal deaths (153/235, 63.0%). Bacterial isolates caused about three-fourths (296/401; 73.8%) of the infections. The two common pathogens-Klebsiella pneumoniae (n = 50, 12.5%) and Acinetobacter baumannii (n = 46, 11.5%)-showed high degree of multi-drug resistance (78.0% and 91.3%, respectively) and carbapenem resistance (84.0% and 91.3%, respectively). About a quarter of infections were caused by Candida spp. (n = 91; 22.7%); almost three-fourths (73.7%) of these infections occurred in neonates born at or after 32 weeks' gestation and about two-thirds (62.1%) in those weighing 1500 g or more at birth.
In this large outborn cohort, we report high burden of sepsis, high prevalence of systemic fungal infections, and alarming rates of antimicrobial resistance among bacterial pathogens.
Aim
To provide comprehensive evidence of the effect of interventions on early initiation, exclusive, continued and any breastfeeding rates when delivered in five settings: (i) Health systems and ...services (ii) Home and family environment (iii) Community environment (iv) Work environment (v) Policy environment or a combination of any of above.
Methods
Of 23977 titles identified through a systematic literature search in PUBMED, Cochrane and CABI, 195 articles relevant to our objective, were included. We reported the pooled relative risk and corresponding 95% confidence intervals as our outcome estimate. In cases of high heterogeneity, we explored its causes by subgroup analysis and meta‐regression and applied random effects model.
Results
Intervention delivery in combination of settings seemed to have higher improvements in breastfeeding rates. Greatest improvements in early initiation of breastfeeding, exclusive breastfeeding and continued breastfeeding rates, were seen when counselling or education were provided concurrently in home and community, health systems and community, health systems and home settings, respectively. Baby friendly hospital support at health system was the most effective intervention to improve rates of any breastfeeding.
Conclusion
To promote breastfeeding, interventions should be delivered in a combination of settings by involving health systems, home and family and the community environment concurrently.
The aim of the study was to evaluate the incidence of peripheral inserted central catheter (PICC) tip malposition when the catheter is inserted under real-time ultrasound (RTUS) guidance when ...compared with conventional landmark (CL) technique in neonates. Additional objectives were to evaluate the PICC longevity and central line associated blood stream infections (CLABSI).
In this randomised controlled trial, neonates were randomised to 'RTUS' (n = 40) or 'CL' (n = 40) groups. PICC tip was placed under ultrasound guidance in lower third of superior vena cava in the RTUS group. In 'CL' group, PICC was inserted as calculated by anatomical landmarks.
The birth weight (1286 (926, 1662) vs. 1061 (889, 1636) g) and gestation (31.12 (3.1) vs. 31.4 (3.6) wks) were comparable among the groups. RTUS guidance during PICC insertion reduced incidence of tip malposition by 52% (67.5 vs. 32.5%; RR: 0.48; 95% CI: 0.29-0.79). The longevity of PICC and episodes of CLABSI were however similar in the two groups.
Real-time ultrasound guidance during PICC placement reduces the incidence of tip malposition.
Fortification of expressed breast milk (EBM) using commercially available human milk fortifiers (HMF) increases short-term weight and length in preterm very low-birth-weight (VLBW) neonates. However, ...the high cost and increased risk of feed intolerance limit their widespread use. Preterm formula powder fortification (PTF) might be a better alternative in resource-limited settings.
To demonstrate that fortification of EBM by preterm formula powder is noninferior to fortification by HMF, in terms of short-term weight gain, in VLBW neonates.
Open-label, noninferiority, randomized trial conducted from December 2017 to June 2019 at a level 3 neonatal unit in India. The trial enrolled preterm (born at or before 34 weeks of gestation) VLBW neonates receiving at least 100 mL/kg/d of feeds and consuming 75% of milk or more as EBM.
Neonates were randomly assigned to receive fortification by either PTF or HMF. Calcium, phosphorus, iron, vitamin D, and multivitamins were supplemented in PTF and only vitamin D in the HMF group to meet the recommended dietary allowances.
The primary outcome was the weight gain until discharge from the hospital or 40 weeks' postmenstrual age, whichever was earlier; the prespecified noninferiority margin was 2 g/kg/d. Secondary outcomes included morbidities such as necrotizing enterocolitis, feed intolerance, and extrauterine growth restriction (<10th percentile on the Fenton chart at 40 weeks' postmenstrual age).
Of the 123 neonates enrolled, 60 and 63 were randomized to the PTF and HMF groups, respectively. The mean gestation (30.5 vs 29.9 weeks) and birth weight (1161 vs 1119 g) were comparable between the groups. There was no difference in the mean (SD) weight gain between the PTF and HMF groups (15.7 3.9 vs 16.3 4.0 g/kg/d; mean difference, -0.5 g/kg/d; 95% CI, -1.9 to 0.7). The lower bound of 95% CI did not cross the noninferiority margin. The incidence of feed intolerance was lower in the PTF group (1.4 vs 6.8 per 1000 patient-days; incidence rate ratio 0.19; 95% CI, 0.04 to 0.95), and fewer neonates required withholding of fortification for 24 hours or more (5% vs 22%; risk ratio, 0.22; 95% CI, 0.07 to 0.75). The incidence of necrotizing enterocolitis stage II or more (0 vs 5%) and extrauterine growth restriction (73% vs 81%) was comparable between the groups.
Fortification with preterm formula powder is not inferior to fortification with human milk fortifiers in preterm neonates. Given the possible reduction in feed intolerance and lower costs, preterm formula might be a better option for fortification, especially in resource-restricted settings.
Clinical Trial Registry, India Identifier: CTRI/2017/11/010593.
To compare the risk of mortality and other clinical outcomes in children with sepsis, severe sepsis, or septic shock who received antibiotics within the first hour of recognition (early antibiotics ...group) with those who received antibiotics after the first hour (delayed antibiotics group).
In this prospective cohort study, we enrolled children <17 years of age presenting to the pediatric emergency and diagnosed with sepsis or septic shock without prior antibiotic therapy. Primary outcome was mortality and the secondary outcomes were day 1 Pediatric Logistic Organ Dysfunction score, ventilator-free days, and hospital-free days. These outcomes were compared between the early and the delayed antibiotic groups. The reference point for defining early and delayed antibiotic groups was time 0, which was measured from the time the patient was diagnosed to have sepsis, severe sepsis, or septic shock to the time of administration of the first dose of antibiotics.
About three-fourths (77%) of the 441 children enrolled had septic shock. A total of 241 (55%) and 200 (45%) children were in the delayed and early antibiotic groups, respectively. Children in the delayed group had significantly higher odds of mortality than those in the early group (29% vs 20%; aOR 1.83; 95% CI, 1.14-2.92; P = .01). The time to shock reversal was significantly shorter, and the ventilator-free days and hospital-free days were significantly greater, in the early antibiotic group. There was no difference between the groups with regard to any of the other clinical outcomes.
Delayed administration of antibiotics beyond 1 hour of recognition was associated with higher mortality rates in children with sepsis, severe sepsis, and septic shock. Antibiotics should be administered within the first hour, along with other resuscitative measures, in these children.
To estimate the prevalence and effects of sepsis-induced myocardial dysfunction (SIMD) in children with septic shock.
Enrolled children with septic shock (n = 31) and sepsis (n = 30) underwent ...echocardiography and cardiac troponin-I (cTnI) estimation within first 3 h. SIMD was defined as presence of systolic/diastolic dysfunction by echocardiography.
The prevalence of SIMD was 71% in 'septic shock' and 23% in 'sepsis'. Diastolic dysfunction (45.2%) was more prevalent than systolic dysfunction (32.3%). Children with SIMD had higher requirement of inotropes 81 vs. 44%; adjusted odds ratio: 1.41 (1.04-1.92) in first 48 h. cTnI had low sensitivity (62.5%) and specificity (55.1%) for detecting SIMD. On follow-up at 3 months, there was no residual dysfunction in the majority (71.3%).
SIMD, especially diastolic dysfunction, is common in septic shock and may increase inotrope requirement. It is reversible in majority. Sepsis patients may have asymptomatic underlying SIMD. cTnI does not correlate with the degree of SIMD.
Purpose
To compare the effect of ‘intermittent’ central venous oxygen saturation (ScvO
2
) monitoring with ‘continuous’ ScvO
2
monitoring on shock resolution and mortality in children with septic ...shock.
Methods
Primary outcome was the achievement of therapeutic goals or shock resolution in the first 6 h. We randomly assigned children < 17 years’ age with septic shock to ‘intermittent ScvO
2
’ or ‘continuous ScvO
2
’ groups. All children were subjected to subclavian/internal jugular line insertion and managed as per Surviving Sepsis Campaign Guidelines. To guide resuscitation, we used ScvO
2
estimated at other clinical and laboratory parameters were monitored similarly in both groups.
Results
We enrolled 75 and 77 children median (IQR) age: 6 (1.5–10) years in the ‘intermittent’ and ‘continuous’ groups, respectively. Baseline characteristics were comparable between the groups. When compared to the ‘continuous’ group, fewer children in the ‘intermittent’ group achieved shock resolution within first 6 h 19% vs. 36%; relative risk (RR) 0.51; 95% CI 0.29–0.89; risk difference − 18.0%; 95% CI − 32.0 to − 4.0. The lower bound of confidence interval, however, crossed the pre-specified non-inferiority margin. There was no difference in the proportion of children attaining shock resolution within 24 h (63% vs. 69%; RR 0.86; 95% CI 0.68–1.08) or risk of mortality between the groups (47% vs. 43%; RR 1.06; 95% CI 0.74–1.51).
Conclusions
Given that a greater proportion of children attained therapeutic end points in the first 6 h, continuous monitoring of ScvO
2
should preferably be used to titrate therapy in the first few hours in children with septic shock. In the absence of such facility, intermittent monitoring of ScvO
2
can be used to titrate therapy in these children, given the lack of difference in the proportion of patients achieving shock resolution at 24 h or in risk of mortality between the intermittent and continuous groups.
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