Comparison of mortality and survival without major morbidities of very preterm infants with very low birth weight from Japan and Brazil / Comparação entre mortalidade e sobrevida sem morbidades importantes dos recém-nascidos prematuros de muito baixo peso entre o Japão e o Brasil

Abstract Objective: This study was carried out to understand the disparities in mortality and survival without major morbidities among very premature and very low birth weight infants between participating Neonatal Intensive Care Units (NICUs) from the Brazilian Network on Neonatal Research (RBPN) and the Neonatal Research Network of Japan (NRNJ). Methods: Secondary data analysis of surveys by the RBPN and NRNJ was performed. The surveys were conducted in 2014 and 2015 and included 187 NICUs. Primary outcome was mortality or survival without any major morbidity. Logistic regression analysis adjustment for confounding factors was used. Results: The study population consisted of 6,406 infants from the NRNJ and 2,319 from the RBPN. Controlling for various confounders, infants from RBPN had 9.06 times higher adjusted odds of mortality (95%CI 7.30-11.29), and lower odds of survival without major morbidities (AOR 0.36; 95%CI 0.32-0.41) compared with those from the NRNJ. Factors associated with higher odds of mortality among Brazilian NICUs included: Air Leak Syndrome (AOR 4.73; 95%CI 1.26-15.27), Necrotizing Enterocolitis (AOR 3.25; 95%CI 1.38-7.26), and Late Onset Sepsis (LOS) (AOR 4.86; 95%CI 2.25-10.97). Conclusions: Very premature and very low birth weight infants from Brazil had significantly higher odds for mortality and lower odds for survival without major morbidities in comparison to those from Japan. Additionally, we identified the factors that increased the odds of in-hospital neonatal death in Brazil, most of which was related to LOS.

RESUMO Objetivo: Este estudo foi realizado para compreender as disparidades na mortalidade e sobrevivência sem as principais morbidades entre recém-nascidos muito prematuros e de muito baixo peso entre Unidades de Terapia Intensiva Neonatal (UTINs) participantes da Rede Brasileira de Pesquisas Neonatais (RBPN) e Rede de Pesquisa Neonatal do Japão (NRNJ). Métodos: Foi realizada uma análise dos dados secundários dos bancos de dados da RBPN e da NRNJ. As pesquisas foram realizadas em 2014 e 2015 e incluíram 187 UTINs. O desfecho primário foi mortalidade ou sobrevida sem qualquer morbidade importante. Utilizou-se a análise de regressão logística com ajuste para os fatores de confusão. Resultados: A população do estudo foi composta por 6.406 recém-nascidos do NRNJ e 2.319 do RBPN. Ajustando para diversos fatores de confusão, os prematuros da RBPN tiveram 9,06 vezes maiores chances de mortalidade (IC95% 7,30-11,29) e menores chances de sobrevivência sem morbidades importantes (AOR 0,36; IC95% 0,32-0,41) em comparação com os da NRNJ. Fatores associados a maiores chances de mortalidade entre as UTINs brasileiras incluíram: síndrome de escape de ar (AOR 4,73; IC95% 1,26-15,27), enterocolite necrosante (AOR 3,25; IC95% 1,38-7,26) e sepse de início tardio (AOR 4,86; IC95% 2,25-10,97). Conclusões: Os recém-nascidos muito prematuros e de muito baixo peso do Brasil apresentaram chances significativamente maiores de mortalidade e menores chances de sobrevivência sem as principais morbidades em comparação aos do Japão. Além disso, identificamos os fatores que aumentam as chances da morte neonatal no Brasil, sendo a maioria relacionada à sepse tardia.

Economic Evaluations of Gestational Diabetes Mellitus Screening: A Systematic Review.

BACKGROUND: This study aims to find evidence of the cost-effectiveness of gestational diabetes mellitus (GDM) screening and assess the quality of current economic evaluations, which have shown different conclusions with a variation in screening methods, data sources, outcome indicators, and implementation in diverse organizational contexts. METHODS: Embase, Medline, Web of Science, Health Technology Assessment, database, and National Health Service Economic Evaluation Database databases were searched through June 2019. Studies on economic evaluation reporting both cost and health outcomes of GDM screening programs in English language were selected, and the quality of the studies was assessed using Drummond's checklist. The general characteristics, main assumptions, and results of the economic evaluations were summarized. RESULTS: Our search yielded 10 eligible economic evaluations with different screening strategies compared in different settings and perspectives. The selected papers scored 81% (68-97%) on the items in Drummond's checklist on average. In general, a screening program is cost-effective or even dominant over no screening. The one-step screening, with more cases detected, is more likely to be cost-effective than the two-step screening. Universal screening is more likely to be cost-effective than screening targeting the high-risk population. Parameters affecting cost-effectiveness include: diagnosis criteria, epidemiological characteristics of the population, efficacy of screening and treatment, and costs. CONCLUSIONS: Most studies found GDM screening to be cost-effective, though uncertainties remain due to many factors. The quality assessment identified weaknesses in the economic evaluations in terms of integrating existing data, measuring costs and consequences, analyzing perspectives, and adjusting for uncertainties.

Secular trends in longevity among people with Down syndrome in Japan, 1995-2016.

BACKGROUND: Life expectancy in Japan has increased dramatically and is one of the longest in the world. However, the changes in lifespan in Japanese individuals with congenital diseases remain unknown. We investigated secular changes in the lifespan of people with Down syndrome over the last 20 years. METHODS: We observed secular trends in the number of stillbirths, deaths and the mortality rates at ages 20, 40, and 60 among all deaths registered with Down syndrome as the cause of death (ICD10 code: Q90) in the Japan national death registry database between 1995 and 2016. Changes in the median age at death between 1995-2005 and 2006-2016 were investigated based on sex and history of surgery. RESULTS: We identified 240 stillbirths and 1,099 deaths in this period. The annual number of stillbirths and deaths above the age of 1 year increased, whereas the number of deaths below 1 year did not change. The proportional mortality indicator at ages 20, 40, and 60 increased from 21.7%, 11.7%, and 1.7% in 1995 to 69.9%, 66.7%, and 36.6% in 2016, respectively. The median age at death was higher in females, individuals without a surgical history, and deaths occurring in 2006-2016. The median age at death increased over the period in those without a surgical history. CONCLUSIONS: The age at death among people with Down syndrome has increased over the last 20 years, with currently 1 in 3 persons living over 60 years, necessitating adequate social welfare services in this aging population.

Autologous cord blood cell therapy for neonatal hypoxic-ischaemic encephalopathy: a pilot study for feasibility and safety.

Neonatal hypoxic-ischaemic encephalopathy (HIE) is a serious condition; many survivors develop neurological impairments, including cerebral palsy and intellectual disability. Preclinical studies show that the systemic administration of umbilical cord blood cells (UCBCs) is beneficial for neonatal HIE. We conducted a single-arm clinical study to examine the feasibility and safety of intravenous infusion of autologous UCBCs for newborns with HIE. When a neonate was born with severe asphyxia, the UCB was collected, volume-reduced, and divided into three doses. The processed UCB was infused at 12-24, 36-48, and 60-72 hours after the birth. The designed enrolment was six newborns. All six newborns received UCBC therapy strictly adhering to the study protocol together with therapeutic hypothermia. The physiological parameters and peripheral blood parameters did not change much between pre- and postinfusion. There were no serious adverse events that might be related to cell therapy. At 30 days of age, the six infants survived without circulatory or respiratory support. At 18 months of age, neurofunctional development was normal without any impairment in four infants and delayed with cerebral palsy in two infants. This pilot study shows that autologous UCBC therapy is feasible and safe.

TNF-α blockers for the treatment of Kawasaki disease in children.

BACKGROUND: Kawasaki disease (KD) is an acute inflammatory vasculitis (inflammation of the blood vessels) that mainly affects children between six months and five years of age. The vasculitis primarily impacts medium-sized blood vessels, especially in the coronary arteries. In most children, intravenous immunoglobulin (IVIG) and aspirin therapy rapidly reduce inflammatory markers, fever, and other clinical symptoms. However, approximately 15% to 20% of children receiving the initial IVIG infusion show persistent or recurrent fever and are classified as IVIG-resistant. Tumor necrosis factor-alpha (TNF-α) is an inflammatory cytokine that plays an important role in host defence against infections and in immune responses. Several studies have established that blocking TNF-α is critical for obtaining anti-inflammatory effects in children with KD, thus, there is a need to identify benefits and risks of TNF-α blockers for the treatment of KD. OBJECTIVES: To evaluate the efficacy and safety of using TNF-α blockers (i.e. infliximab and etanercept) to treat children with Kawasaki disease. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials register to 19 September 2018. We also undertook reference checking of grey literature. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared TNF-α blockers (i.e. infliximab and etanercept) to placebo or other drugs (including retreatment with IVIG) in children with KD, reported in abstract or full-text. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the study selection criteria, assessed risk of bias and extracted data. When necessary, we contacted study authors for additional information. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included five trials from 14 reports, with a total of 494 participants. All included trials were individual RCTs that examined the effect of TNF-α blockers for KD.Five trials (with 494 participants) reported the incidence of treatment resistance. TNF-α blockers reduced the incidence of treatment resistance (TNF-α blocker intervention group 30/237, control group 58/257; risk ratio (RR) 0.57, 95% confidence interval (CI) 0.38 to 0.86; low-certainty evidence).Four trials reported the incidence of coronary artery abnormalities (CAAs). Three trials (with 270 participants) contributed data to the meta-analysis, since we could not get the data needed for the analysis from the fourth trial. There was no clear difference between groups in the incidence of CAAs (TNF-α blocker intervention group 8/125, control group 9/145; RR 1.18, 95% CI 0.45 to 3.12; low-certainty evidence).Three trials with 250 participants reported the adverse effect 'infusion reactions' after treatment initiation. The TNF-α blocker intervention decreased infusion reactions (TNF-α blocker intervention group 0/126, control group 15/124; RR 0.06, 95% CI 0.01 to 0.45; low-certainty evidence).Two trials with 227 participants reported the adverse effect 'infections' after treatment initiation. There was no clear difference between groups (TNF-α blocker intervention group 7/114, control group 10/113; RR 0.68, 95% CI 0.33 to 1.37; low-certainty evidence).One trial (with 31 participants) reported the adverse effect 'cutaneous reactions' (rash and contact dermatitis). There was no clear difference between the groups for incidence of rash (TNF-α blocker intervention group 2/16, control group 0/15; RR 4.71, 95% CI 0.24 to 90.69; very low-certainty evidence) or for incidence of contact dermatitis (TNF-α blocker intervention group 1/16, control group 3/15; RR 0.31, 95% CI 0.04 to 2.68; very low-certainty evidence).No trials reported other adverse effects such as injection site reactions, neutropenia, infections, demyelinating disease, heart failure, malignancy, and induction of autoimmunity. AUTHORS' CONCLUSIONS: We found a limited number of RCTs examining the effect of TNF-α blockers for KD. In summary, low-certainty evidence indicates that TNF-α blockers have beneficial effects on treatment resistance and the adverse effect 'infusion reaction' after treatment initiation for KD when compared with no treatment or additional treatment with IVIG. Further research will add to the evidence base. Due to the small number of underpowered trials contributing to the analyses, the results presented should be treated with caution. Further large high quality trials with timing and type of TNF-α blockers used are needed to determine the effects of TNF-α blockers for KD.

A scoping review of palliative care for children in low- and middle-income countries.

BACKGROUND: Ninety-eight percent of children needing palliative care live in low- and middle-income countries (LMICs), and almost half of them live in Africa. In contrast to the abundance of data on populations in high income countries, the current data on populations in LMICs is woefully inadequate. This study aims to identify and summarize the published literature on the need, accessibility, quality, and models for palliative care for children in LMICs. METHODS: A scoping review was performed following the method of Arksey and O'Malley. Systematic searches were conducted on PubMed and Google Scholar using the main keywords, 'children AND palliative care OR terminal care OR hospice OR end of life AND developing countries OR LMICs.' Additional publications were obtained by handsearching. Papers were only included if they reported on the need, accessibility, quality, and models for palliative care for children in LMICs. RESULTS: Fifteen papers met the inclusion criteria for review. Of these, 10 assessed need, seven examined availability and/or accessibility, one assessed quality, and one examined the models. We found an urgent need for palliative care, particularly in the training for health workers and improving poor availability and/or accessibility to palliative care in terms of factors such as medication and bereavement support. The best practice models demonstrated feasibility and sustainability through cooperation with governments and community organizations. The quality of pain management and emotional support was lower in LMICs compared to HICs. CONCLUSION: Although we found limited evidence in this review, we identified common challenges such as the need for further training for health workers and greater availability of opioid analgesics. While efforts to change the current systems and laws applying to children in LMICs are important, we should also tackle underlying factors including the need to raise awareness about palliative care in public health and improve the accuracy of data collection.

Effects of the early administration of sivelestat sodium on bronchopulmonary dysplasia in infants: A retrospective cohort study.

BACKGROUND: Chorioamnionitis, or infiltration of the chorioamnion by neutrophils, is a risk factor associated with the development of bronchopulmonary dysplasia. Increased neutrophil elastase levels are observed in the tracheal aspirates of these patients. AIMS: To examine the effects of early administration of the selective neutrophil elastase inhibitor sivelestat, which is used to treat acute lung injury in adults, on bronchopulmonary dysplasia in extremely premature infants. STUDY DESIGN: Retrospective cohort study. SUBJECTS: This study included extremely low-birth-weight infants born at a gestational age<28weeks. Patients were divided into groups based on the receipt of sivelestat. OUTCOME MEASURES: The primary outcome was the rate of bronchopulmonary dysplasia-free survival at a postmenstrual age of 36weeks, and the secondary outcomes included various clinically significant factors of neonatal mortality and morbidity and adverse events. RESULTS: Of the 1031 included neonates, 124 (12.0%) were treated with sivelestat. Significant differences between the groups were noted for gestational age, delivery method, fetal number, the frequency of chorioamnionitis, immunoglobulin M levels, and WBC counts. No differences were identified concerning the bronchopulmonary dysplasia-free survival rate at a postmenstrual age of 36weeks (adjusted odds ratio for sivelestat to control, 0.83; 95% confidence interval=0.53-1.30). Secondary outcomes did not significantly differ between the groups. CONCLUSIONS: In extremely premature infants, early sivelestat use was not associated with an improved rate of survival without bronchopulmonary dysplasia at a postmenstrual age of 36weeks.

Cost-effectiveness analysis of different types of human papillomavirus vaccination combined with a cervical cancer screening program in mainland China.

BACKGROUND: China has a high prevalence of human papillomavirus (HPV) and a consequently high burden of disease with respect to cervical cancer. The HPV vaccine has proved to be effective in preventing cervical cancer and is now a part of routine immunization programs worldwide. It has also proved to be cost effective. This study aimed to assess the cost-effectiveness of 2-, 4-, and 9-valent HPV vaccines (hereafter, HPV2, 4 or 9) combined with current screening strategies in China. METHODS: A Markov model was developed for a cohort of 100,000 HPV-free girls to simulate the natural history to HPV infection. Three recommended screening methods (1. liquid-based cytology test + HPV DNA test; 2. pap smear cytology test + HPV DNA test; 3. visual inspection with acetic acid) and three types of HPV vaccination program (HPV2/4/9) were incorporated into 15 intervention options, and the incremental cost-effectiveness ratio (ICER) was calculated to determine the dominant strategies. Costs, transition probabilities and utilities were obtained from a review of the literature and national databases. One-way sensitivity analyses and threshold analyses were performed for key variables in different vaccination scenarios. RESULTS: HPV9 combined with screening showed the highest health impact in terms of reducing HPV-related diseases and increasing the number of quality-adjusted life years (QALYs). Under the current thresholds of willingness to pay (WTP, 3 times the per capita GDP or USD$ 23,880), HPV4/9 proved highly cost effective, while HPV2 combined with screening cost more and was less cost effective. Only when screening coverage increased to 60% ~ 70% did the HPV2 and screening combination strategy become economically feasible. CONCLUSIONS: The combination of the HPV4/9 vaccine with current screening strategies for adolescent girls was highly cost-effective and had a significant impact on reducing the HPV infection-related disease burden in Mainland China.

Updated comprehensive epidemiology, microbiology, and outcomes among patients with acute cholangitis.

BACKGROUND: The international practice guidelines for patients with acute cholangitis and cholecystitis were released in 2007 (TG07) and revised in 2013 (TG13). This study investigated updated epidemiology and outcomes among patients with acute cholangitis on a larger scale for the first time. METHODS: This is an international multi-center retrospective observational study in Japan and Taiwan. All consecutive patients older than 18 years of age and given a clinical diagnosis of acute cholangitis by clinicians between 1 January 2011 and 31 December 2012 were enrolled. Those who met the diagnostic criteria of acute cholangitis by TG13 were statistically analyzed. RESULTS: A total of 7,294 patients were enrolled and 6,433 patients met the TG13 diagnostic criteria. The severity distribution was Grade I (37.5%), Grade II (36.2%), and Grade III (26.2%). The 30-day all-cause mortality was 2.4%, 4.7%, and 8.4% in Grade I, II, III severity, respectively (P < 0.001). The incidence of liver abscess and endocarditis as complications of acute cholangitis was 2.0% and 0.26%, respectively. CONCLUSIONS: This is the first large scale study to investigate patients with acute cholangitis. This study provides the basis to define the best practices to manage patients with acute cholangitis in future studies.

Optimal treatment strategy for acute cholecystitis based on predictive factors: Japan-Taiwan multicenter cohort study.

BACKGROUND: Although early laparoscopic cholecystectomy is widely performed for acute cholecystitis, the optimal timing of a cholecystectomy in clinically ill patients remains controversial. This study aims to determine the best practice for the patients presenting with acute cholecystitis focused on disease severity and comorbidities. METHODS: An international multicentric retrospective observational study was conducted over a 2-year period. Patients were divided into four groups: Group A: primary cholecystectomy; Group B: cholecystectomy after gallbladder drainage; Group C: gallbladder drainage alone; and Group D: medical treatment alone. RESULTS: The subjects of analyses were 5,329 patients. There were statistically significant differences in mortality rates between patients with Charlson comorbidity index (CCI) scores below and above 6 (P < 0.001). The shortest operative time was observed in Group A patients who underwent surgery 0-3 days after admission (P < 0.01). Multiple regression analysis revealed CCI and low body mass index <20 as predictive factors of 30-day mortality in Grade I+II patients. Also, jaundice, neurological dysfunction, and respiratory dysfunction were predictive factors of 30-day mortality in Grade III patients. In Grade III patients without predictive factors, there were no difference in mortality between Group A and Group B (0% vs. 0%), whereas Group A patients had higher mortality rates than that of Group B patients (9.3% vs. 0.0%) in cases with at least one predictive factor. CONCLUSION: Even patients with Grade III severity, primary cholecystectomy can be performed safely if they have no predictive factors of mortality. Gallbladder drainage may have a therapeutic role in subgroups with higher CCI or higher disease severity.

Clinical application and verification of the TG13 diagnostic and severity grading criteria for acute cholangitis: an international multicenter observational study.

BACKGROUND: The Tokyo Guidelines 2007 (TG07) first presented the diagnostic and severity grading criteria for acute cholangitis. Subsequently updated in 2013, the Tokyo Guidelines (TG13) have been widely adopted throughout the world as global standard guidelines. We set out to verify the efficacy of these TG13 criteria in an international multicenter study. METHODS: We reviewed 6,063 patients who were clinically diagnosed with acute cholangitis in Japan and Taiwan over a 2-year period. The TG13 diagnostic and severity grading criteria were retrospectively applied, and 30-day mortality was investigated. RESULTS: A diagnosis of acute cholangitis was made in 5,454 (90.0%) patients on the basis of the TG13 criteria, and in 4,815 (79.4%) patients on the basis of the TG07 criteria. The 30-day mortality rates of patients with Grade III, Grade II, and Grade I were 5.1%, 2.6%, and 1.2%, respectively, and increased significantly along with disease severity. The mortality rate in the 1,272 Grade II cases where urgent or early biliary drainage was performed was 2.0% (n = 25), which was significantly lower than that of 3.7% (n = 28) in the other 748 cases. CONCLUSION: By using the TG13 diagnostic and severity grading criteria, more patients with possible acute cholangitis can be diagnosed, and patients whose prognosis can potentially be improved by early biliary drainage can be identified. The TG13 criteria are appropriate and useful for clinical practice.

Validation of TG13 severity grading in acute cholecystitis: Japan-Taiwan collaborative study for acute cholecystitis.

BACKGROUND: The collaborative multicenter retrospective study of acute cholecystitis (AC) was performed in Japan and Taiwan. The aim for this study was evaluation of the clinical value of TG13 severity grading for AC. METHOD: The study was designed as an international multicenter retrospective study of AC from 2011 to 2013. Based on the data, we investigated the TG13 severity grading by analyzing the correlations between grade and prognosis, surgical procedures, histopathology, and organ dysfunction and prognosis. RESULTS: An investigation revealed that 30-day overall mortality rate was 1.1% for Grade I, 0.8% for Grade II, 5.4% for Grade III. The mortality rate for Grade III was significantly higher than lower grades (P < 0.001). The greater the number of organ dysfunction, the higher the mortality rate (P < 0.001). However, the mortality rate varied depending on the number of organ dysfunction (3.1-25%). With respect to the surgical procedures, laparoscopic cholecystectomy was performed for Grade I patients (P < 0.001), and the higher the grade, the more likely open surgery would be selected (P < 0.001). CONCLUSION: TG13 severity grading criteria for AC are providing great benefits in actual clinical settings. From this study, the position of each severity grade was obviously confirmed.

Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus.

The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and/or neurosensory outcomes reported moderate-to-low predictive values regardless of the BPD criteria. CONCLUSION: A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.

Neonatal Outcomes of Very Low Birth Weight and Very Preterm Neonates: An International Comparison.

OBJECTIVE: To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN: We included 58 004 infants born weighing <1500 g at 24(0)-31(6) weeks' gestation from databases in Australia/New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the United Kingdom. We compared a composite outcome (mortality or any of grade ≥3 peri-intraventricular hemorrhage, periventricular echodensity/echolucency, bronchopulmonary dysplasia, or treated retinopathy of prematurity) between each country and all others by using standardized ratios and pairwise using logistic regression analyses. RESULTS: Despite differences in population coverage, included neonates were similar at baseline. Composite outcome rates varied from 26% to 42%. The overall mortality rate before discharge was 10% (range: 5% [Japan]-17% [Spain]). The standardized ratio (99% CIs) estimates for the composite outcome were significantly greater for Spain 1.09 (1.04-1.14) and the United Kingdom 1.16 (1.11-1.21), lower for Australia/New Zealand 0.93 (0.89-0.97), Japan 0.89 (0.86-0.93), Sweden 0.81 (0.73-0.90), and Switzerland 0.77 (0.69-0.87), and nonsignificant for Canada 1.04 (0.99-1.09) and Israel 1.00 (0.93-1.07). The adjusted odds of the composite outcome varied significantly in pairwise comparisons. CONCLUSIONS: We identified marked variations in neonatal outcomes between countries. Further collaboration and exploration is needed to reduce variations in population coverage, data collection, and case definitions. The goal would be to identify care practices and health care organizational factors, which has the potential to improve neonatal outcomes.

Hospitalization risk factors for children's lower respiratory tract infection: A population-based, cross-sectional study in Mongolia.

This study aimed to assess the potential risk factors for lower respiratory tract infection (LRTI)-related hospital admissions in Mongolian children. A population-based cross-sectional study was conducted in rural Mongolia in 2013, and 1,013 mother-child pairs were included. Of the participating children, 38.9% were admitted to hospital with LRTIs. Home smoking, low birthweight, being a male child, exclusive breastfeeding and healthcare-seeking behaviour showed substantial association with LRTI-related hospital admissions. Number of cigarettes smoked by family members showed a dose-response relationship and increased hospital admissions. Strategies to prevent second-hand-smoke exposure from adult smokers, especially inside the home, are crucial to preventing LRTI-related hospital admissions for children in Mongolia. Improving rates of exclusive breastfeeding and increasing birthweight have great potential to decrease the likelihood of children acquiring a LRTI. Educational initiatives are also necessary for women who are less likely to seek out care for their children's symptoms.

Prophylactic antibiotics for manual removal of retained placenta during vaginal birth: a systematic review of observational studies and meta-analysis.

BACKGROUND: Manual removal of the placenta is an invasive obstetric procedure commonly used for the management of retained placenta. However, it is unclear whether antibiotic prophylaxis is beneficial in preventing infectious morbidity. We conducted a systematic review to determine the efficacy and safety of routine use of antibiotics for preventing adverse maternal outcomes related to manual placenta removal following vaginal birth. METHODS: A detailed search of MEDLINE, EMBASE, Cochrane library and the CINAHL databases was conducted for non-randomized studies involving women undergoing manual placenta delivery after vaginal births and where antibiotic prophylaxis use was compared with no treatment or placebo to prevent maternal infection. Search terms including 'delivery, obstetric', 'placenta, retained', 'anti-infective agents', and 'chemoprevention' were used. RESULTS: Of the 407 citations that resulted after elimination of duplicates, 81 full texts were potentially eligible after independent assessment of the title and abstracts. Independent review of the full texts identified three eligible cohort studies which were retrospective in design. These studies contained data on two of the pre-specified outcomes, endometritis and puerperal fever. Other secondary outcomes such as perineal infection and/or any infection, hospital stay duration, sepsis, hemorrhage >1000 ml or hospital readmissions were not reported on excluding puerperal fever. A meta-analysis showed no significant reduction in the incidence of endometritis (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.38 to 1.85, three studies, 567 women) and puerperal fever (OR 0.99, 95% CI 0.38 to 2.27, one study, 302 women). CONCLUSIONS: There is currently no evidence to suggest beneficial effects for routine antibiotic use in women undergoing manual placental removal following vaginal birth. In appropriate settings, further research is required to determine whether a policy of routine antibiotic prophylaxis for the procedure should be maintained or discouraged.

Giving women their own case notes to carry during pregnancy.

BACKGROUND: In many countries women are given their own case notes to carry during pregnancy to increase their sense of control over, and satisfaction with, their care. OBJECTIVES: To evaluate the effects of giving women their own case notes to carry during pregnancy. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials of women given their own case notes to carry during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and assessed study quality. One review author extracted data from the included studies using a standard form (checked by second review author). We assessed estimates of effect using risk ratio (RR) with 95% confidence intervals (CI). The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Four trials were included (n = 1176 women). Overall, the quality of the evidence was graded as low to moderate mainly due to the nature of the intervention not allowing blinding. The updated search identified one cluster-randomised trial, which was included.Women carrying their own notes were more likely to feel in control (two trials, RR 1.56, 95% CI 1.18 to 2.06; 450 women; moderate quality evidence), although there is no evidence of difference in women's satisfaction (two trials, average RR 1.09, 95% CI 0.92 to 1.29); 698 women; low quality evidence). More women in the case notes group wanted to carry their own notes in a subsequent pregnancy (three trials, RR 1.79, 95% CI 1.57 to 2.03; 552 women; low quality evidence). Overall, the pooled estimate of the two trials (n = 347) that reported on the risk of notes lost or left at home was not significant (average RR 0.38, 95% CI 0.04 to 3.84). There was no evidence of difference for health-related behaviours (cigarette smoking and breastfeeding (moderate quality evidence)), analgesia needs during labour (low quality evidence), maternal depression, miscarriage, stillbirth and neonatal deaths (moderate quality evidence). More women in the case notes group had operative deliveries (one trial, RR 1.83, 95% CI 1.08 to 3.12; 212 women), and caesarean sections (one trial, average RR 1.51, 95% CI 1.10 to 2.08; 501 women; moderate quality evidence). AUTHORS' CONCLUSIONS: The four trials are small, and not all of them reported on all outcomes. The results suggest that there are both potential benefits (increased maternal control and increased availability of antenatal records during hospital attendance) and harms (more operative deliveries). Importantly, all of the trials report that more women in the case notes group would prefer to carry their antenatal records in another pregnancy. There is insufficient evidence on health-related behaviours (smoking and breastfeeding), women's satisfaction, and clinical outcomes. It is important to emphasise that this review shows a lack of evidence of benefit rather than evidence of no benefit.

Antenatal dietary education and supplementation to increase energy and protein intake.

BACKGROUND: Gestational weight gain is positively associated with fetal growth, and observational studies of food supplementation in pregnancy have reported increases in gestational weight gain and fetal growth. OBJECTIVES: To assess the effects of education during pregnancy to increase energy and protein intake, or of actual energy and protein supplementation, on energy and protein intake, and the effect on maternal and infant health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015), reference lists of retrieved studies and contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials of dietary education to increase energy and protein intake, or of actual energy and protein supplementation, during pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed risk of bias. Two review authors independently extracted data and checked for accuracy. Extracted data were supplemented by additional information from the trialists we contacted. MAIN RESULTS: We examined 149 reports corresponding to 65 trials. Of these trials, 17 were included, 46 were excluded, and two are ongoing. Overall, 17 trials involving 9030 women were included. For this update, we assessed methodological quality of the included trials using the standard Cochrane criteria (risk of bias) and the GRADE approach. The overall risk of bias was unclear. Nutritional education (five trials, 1090 women) Women given nutritional education had a lower relative risk of having a preterm birth (two trials, 449 women) (risk ratio (RR) 0.46, 95% CI 0.21 to 0.98, low-quality evidence), and low birthweight (one trial, 300 women) (RR 0.04, 95% CI 0.01 to 0.14). Head circumference at birth was increased in one trial (389 women) (mean difference (MD) 0.99 cm, 95% CI 0.43 to 1.55), while birthweight was significantly increased among undernourished women in two trials (320 women) (MD 489.76 g, 95% CI 427.93 to 551.59, low-quality evidence), but did not significantly increase for adequately nourished women (MD 15.00, 95% CI -76.30 to 106.30, one trial, 406 women). Protein intake increased significantly (three trials, 632 women) (protein intake: MD +6.99 g/day, 95% CI 3.02 to 10.97). No significant differences were observed on any other outcomes such as neonatal death (RR 1.28, 95% CI 0.35 to 4.72, one trial, 448 women, low-quality evidence), stillbirth (RR 0.37, 95% CI 0.07 to 1.90, one trial, 431 women, low-quality evidence), small-for-gestational age (RR 0.97, 95% CI 0.45 to 2.11, one trial, 404 women, low-quality evidence) and total gestational weight gain (MD -0.41, 95% CI -4.41 to 3.59, two trials, 233 women). There were no data on perinatal death. Balanced energy and protein supplementation (12 trials, 6705 women)Risk of stillbirth was significantly reduced for women given balanced energy and protein supplementation (RR 0.60, 95% CI 0.39 to 0.94, five trials, 3408 women, moderate-quality evidence), and the mean birthweight was significantly increased (random-effects MD +40.96 g, 95% CI 4.66 to 77.26, Tau² = 1744, I² = 44%, 11 trials, 5385 women, moderate-quality evidence). There was also a significant reduction in the risk of small-for-gestational age (RR 0.79, 95% CI 0.69 to 0.90, I² = 16%, seven trials, 4408 women, moderate-quality evidence). No significant effect was detected for preterm birth (RR 0.96, 95% CI 0.80 to 1.16, five trials, 3384 women, moderate-quality evidence) or neonatal death (RR 0.68, 95% CI 0.43 to 1.07, five trials, 3381 women, low-quality evidence). Weekly gestational weight gain was not significantly increased (MD 18.63, 95% CI -1.81 to 39.07, nine trials, 2391 women, very low quality evidence). There were no data reported on perinatal death and low birthweight. High-protein supplementation (one trial, 1051 women)High-protein supplementation (one trial, 505 women), was associated with a significantly increased risk of small-for-gestational age babies (RR 1.58, 95% CI 1.03 to 2.41, moderate-quality evidence). There was no significant effect for stillbirth (RR 0.81, 95% CI 0.31 to 2.15, one trial, 529 women), neonatal death (RR 2.78, 95% CI 0.75 to 10.36, one trial, 529 women), preterm birth (RR 1.14, 95% CI 0.83 to 1.56, one trial, 505 women), birthweight (MD -73.00, 95% CI -171.26 to 25.26, one trial, 504 women) and weekly gestational weight gain (MD 4.50, 95% CI -33.55 to 42.55, one trial, 486 women, low-quality evidence). No data were reported on perinatal death. Isocaloric protein supplementation (two trials, 184 women)Isocaloric protein supplementation (two trials, 184 women) had no significant effect on birthweight (MD 108.25, 95% CI -220.89 to 437.40) and weekly gestational weight gain (MD 110.45, 95% CI -82.87 to 303.76, very low-quality evidence). No data reported on perinatal mortality, stillbirth, neonatal death, small-for-gestational age, and preterm birth. AUTHORS' CONCLUSIONS: This review provides encouraging evidence that antenatal nutritional education with the aim of increasing energy and protein intake in the general obstetric population appears to be effective in reducing the risk of preterm birth, low birthweight, increasing head circumference at birth, increasing birthweight among undernourished women, and increasing protein intake. There was no evidence of benefit or adverse effect for any other outcome reported.Balanced energy and protein supplementation seems to improve fetal growth, and may reduce the risk of stillbirth and infants born small-for-gestational age. High-protein supplementation does not seem to be beneficial and may be harmful to the fetus. Balanced-protein supplementation alone had no significant effects on perinatal outcomes.The results of this review should be interpreted with caution. The risk of bias was either unclear or high for at least one category examined in several of the included trials, and the quality of the evidence was low for several important outcomes. Also, as the anthropometric characteristics of the general obstetric population is changing, those developing interventions aimed at altering energy and protein intake should ensure that only those women likely to benefit are included. Large, well-designed randomised trials are needed to assess the effects of increasing energy and protein intake during pregnancy in women whose intake is below recommended levels.

Obstetric transition in the World Health Organization Multicountry Survey on Maternal and Newborn Health: exploring pathways for maternal mortality reduction / Transición obstétrica en la Encuesta Global de la Organización Mundial de la Salud sobre Salud Materna y Neonatal: exploración de las vías de reducción de la mortalidad materna

OBJECTIVE: To test whether the proposed features of the Obstetric Transition Model-a theoretical framework that may explain gradual changes that countries experience as they eliminate avoidable maternal mortality-are observed in a large, multicountry, maternal and perinatal health database; and to discuss the dynamic process of maternal mortality reduction using this model as a theoretical framework. METHODS: This was a secondary analysis of a cross-sectional study by the World Health Organization that collected information on more than 300 000 women who delivered in 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East, during a 2-4-month period in 2010-2011. The ratios of Potentially Life-Threatening Conditions, Severe Maternal Outcomes, Maternal Near Miss, and Maternal Death were estimated and stratified by stages of obstetric transition. The characteristics of each stage are defined. RESULTS: Data from 314 623 women showed that female fertility, indirectly estimated by parity, was higher in countries at a lower obstetric transition stage, ranging from a mean of 3 children in Stage II to 1.8 children in Stage IV. Medicalization increased with obstetric transition stage. In Stage IV, women had 2.4 times the cesarean deliveries (15.3% in Stage II and 36.7% in Stage IV) and 2.6 times the labor inductions (7.1% in Stage II and 18.8% in Stage IV) as women in Stage II. The mean age of primiparous women also increased with stage. The occurrence of uterine rupture had a decreasing trend, dropping by 5.2 times, from 178 to 34 cases per 100 000 live births, as a country transitioned from Stage II to IV. CONCLUSIONS: This analysis supports the concept of obstetric transition using multicountry data. The Obstetric Transition Model could provide justification for customizing strategies for reducing maternal mortality according to a country's stage in the obstetric transition.

RESUMEN OBJETIVO: Evaluar si las características propuestas del Modelo de Transición Obstétrica, un marco teórico que puede explicar los cambios graduales que experimentan los países a medida que eliminan la mortalidad materna evitable, se pueden observar en una amplia base de datos de salud materna y perinatal de varios países; y tratar sobre el proceso dinámico de reducción de la mortalidad materna utilizando este modelo como marco teórico. MÉTODOS: Este estudio consistió en un análisis secundario de un estudio transversal realizado por la Organización Mundial de la Salud que recopiló información sobre más de 300 000 mujeres que dieron a luz en 359 establecimientos de salud de 29 países de África, Asia, América Latina y Oriente Medio, durante un período de 2 a 4 meses en el 2010 y el 2011. Se calcularon los índices de afecciones potencialmente mortales, resultados maternos graves, morbilidad materna extremadamente grave, y muerte materna, y se estratificaron según las etapas de transición obstétrica. Se definen las características de cada etapa. RESULTADOS: Los datos de 314 623 mujeres indicaron que la fecundidad femenina, calculada indirectamente por el número de partos, fue mayor en los países que se hallaban en las primeras etapas de la transición obstétrica, desde un promedio de 3 hijos en el estadio II a 1,8 en el estadio IV. El nivel de medicalización de los establecimientos de salud de los países participantes, definido por el número de partos por cesárea y el número de partos inducidos, tuvo tendencia a aumentar según avanzaba la etapa de transición obstétrica. En el estadio IV, las mujeres tuvieron 2,4 veces más partos por cesárea (15,3% en el estadio II y 36,7% en el estadio IV) y 2,6 veces más inducciones de parto (7,1% en el estadio II y 18,8% en el estadio IV) que las mujeres en el estadio II. A medida que avanzaban las etapas de transición obstétrica, también se incrementaba la media de edad de las mujeres primíparas. La ocurrencia de rotura uterina mostraba una tendencia descendente, y se reducía 5,2 veces, de 178 a 34 casos por 100 000 nacidos vivos, a medida que un país efectuaba la transición del estadio II al IV. CONCLUSIONES: Este análisis apoya el concepto de transición obstétrica utilizando datos de varios países. El Modelo de Transición Obstétrica podría justificar la adaptación de las estrategias para reducir la mortalidad materna según la etapa de transición obstétrica en que se halla un país.

Patent ductus arteriosus management and outcomes in Japan and Canada: comparison of proactive and selective approaches.

OBJECTIVE: The aim of this study is to compare patent ductus arteriosus (PDA) management strategies and outcomes between the Neonatal Research Network of Japan (NRNJ) with proactive functional echocardiography and the Canadian Neonatal Network (CNN) with selective conventional echocardiography practice. STUDY DESIGN: Retrospective analyses examined very low-birth-weight infants admitted to the NRNJ or CNN in 2006 to 2008. Multivariable logistic regression analyses compared a composite outcome indicating a mortality or major morbidity (severe intraventricular hemorrhage, periventricular leukomalacia, severe retinopathy of prematurity, bronchopulmonary dysplasia, or necrotizing enterocolitis) between networks, according to PDA diagnosis and treatment, and tested the association between PDA treatment and the composite outcome within networks. RESULTS: PDA treatment (NRNJ:CNN) with conservative management (8%:16%), indomethacin only (77%:59%), ligation only (1%:13%), or indomethacin and ligation (14%:13%) varied significantly between networks. The composite outcome was lower in NRNJ versus CNN only among infants with PDA (odds ratio: 0.70; 95% confidence interval: 0.62-0.80). Surgical ligation was associated with higher composite outcome only in CNN (odds ratio: 1.79; 95% confidence interval: 1.40-2.28). CONCLUSION: Lower composite mortality/morbidity outcome in Japan versus Canada only among infants with PDA, and association of surgical ligation with higher mortality/morbidity only in Canada, suggest differential PDA management and ligation processes contribute to outcome variation.