Reducing Neonatal Mortality in India: Critical Role of Access to Emergency Obstetric Care

Background

Neonatal mortality currently accounts for 41% of all global deaths among children below five years. Despite recording a 33% decline in neonatal deaths between 2000 and 2009, about 900,000 neonates died in India in 2009. The decline in neonatal mortality is slower than in the post-neonatal period, and neonatal mortality rates have increased as a proportion of under-five mortality rates. Neonatal mortality rates are higher among rural dwellers of India, who make up at least two-thirds of India''s population. Identifying the factors influencing neonatal mortality will significantly improve child survival outcomes in India.

Methods

Our analysis is based on household data from the nationally representative 2008 Indian District Level Household Survey (DLHS-3). We use probit regression techniques to analyse the links between neonatal mortality at the household level and households'' access to health facilities. The probability of the child dying in the first month of birth is our dependent variable.

Results

We found that 80% of neonatal deaths occurred within the first week of birth, and that the probability of neonatal mortality is significantly lower when the child''s village is closer to the district hospital (DH), suggesting the critical importance of specialist hospital care in the prevention of newborn deaths. Neonatal deaths were lower in regions where emergency obstetric care was available at the District Hospitals. We also found that parental schooling and household wealth status improved neonatal survival outcomes.

Conclusions

Addressing the main causes of neonatal deaths in India – preterm deliveries, asphyxia, and sepsis – requires adequacy of specialised workforce and facilities for delivery and neonatal intensive care and easy access by mothers and neonates. The slow decline in neonatal death rates reflects a limited attention to factors which contribute to neonatal deaths. The suboptimal quality and coverage of Emergency Obstetric Care facilities in India require urgent attention.     

Serological Diagnosis of Paracoccidioidomycosis: High Rate of Inter-laboratorial Variability among Medical Mycology Reference Centers

Background

Serological tests have long been established as rapid, simple and inexpensive tools for the diagnosis and follow-up of PCM. However, different protocols and antigen preparations are used and the few attempts to standardize the routine serological methods have not succeeded.

Methodology/Principal findings

We compared the performance of six Brazilian reference centers for serological diagnosis of PCM. Each center provided 30 sera of PCM patients, with positive high, intermediate and low titers, which were defined as the “reference” titers. Each center then applied its own antigen preparation and serological routine test, either semiquantitative double immunodifusion or counterimmmunoelectrophoresis, in the 150 sera from the other five centers blindly as regard to the “reference” titers. Titers were transformed into scores: 0 (negative), 1 (healing titers), 2 (active disease, low titers) and 3 (active disease, high titers) according to each center''s criteria. Major discordances were considered between scores indicating active disease and scores indicating negative or healing titers; such discordance when associated with proper clinical and other laboratorial data, may correspond to different approaches to the patient''s treatment. Surprisingly, all centers exhibited a high rate of “major” discordances with a mean of 31 (20%) discordant scores. Alternatively, when the scores given by one center to their own sera were compared with the scores given to their sera by the remaining five other centers, a high rate of major discordances was also found, with a mean number of 14.8 sera in 30 presenting a discordance with at least one other center. The data also suggest that centers that used CIE and pool of isolates for antigen preparation performed better.

Conclusion

There are inconsistencies among the laboratories that are strong enough to result in conflicting information regarding the patients'' treatment. Renewed efforts should be promoted to improve standardization of the serological diagnosis of PCM.     

Quantifying Spatial Disparities in Neonatal Mortality Using a Structured Additive Regression Model

Background

Neonatal mortality contributes a large proportion towards early childhood mortality in developing countries, with considerable geographical variation at small areas within countries.

Methods

A geo-additive logistic regression model is proposed for quantifying small-scale geographical variation in neonatal mortality, and to estimate risk factors of neonatal mortality. Random effects are introduced to capture spatial correlation and heterogeneity. The spatial correlation can be modelled using the Markov random fields (MRF) when data is aggregated, while the two dimensional P-splines apply when exact locations are available, whereas the unstructured spatial effects are assigned an independent Gaussian prior. Socio-economic and bio-demographic factors which may affect the risk of neonatal mortality are simultaneously estimated as fixed effects and as nonlinear effects for continuous covariates. The smooth effects of continuous covariates are modelled by second-order random walk priors. Modelling and inference use the empirical Bayesian approach via penalized likelihood technique. The methodology is applied to analyse the likelihood of neonatal deaths, using data from the 2000 Malawi demographic and health survey. The spatial effects are quantified through MRF and two dimensional P-splines priors.

Results

Findings indicate that both fixed and spatial effects are associated with neonatal mortality.

Conclusions

Our study, therefore, suggests that the challenge to reduce neonatal mortality goes beyond addressing individual factors, but also require to understanding unmeasured covariates for potential effective interventions.     

Measuring Unsafe Abortion-Related Mortality: A Systematic Review of the Existing Methods

Background

The WHO estimates that 13% of maternal mortality is due to unsafe abortion, but challenges with measurement and data quality persist. To our knowledge, no systematic assessment of the validity of studies reporting estimates of abortion-related mortality exists.

Study Design

To be included in this study, articles had to meet the following criteria: (1) published between September 1^st, 2000-December 1^st, 2011; (2) utilized data from a country where abortion is “considered unsafe”; (3) specified and enumerated causes of maternal death including “abortion”; (4) enumerated ≥100 maternal deaths; (5) a quantitative research study; (6) published in a peer-reviewed journal.

Results

7,438 articles were initially identified. Thirty-six studies were ultimately included. Overall, studies rated “Very Good” found the highest estimates of abortion related mortality (median 16%, range 1–27.4%). Studies rated “Very Poor” found the lowest overall proportion of abortion related deaths (median: 2%, range 1.3–9.4%).

Conclusions

Improvements in the quality of data collection would facilitate better understanding global abortion-related mortality. Until improved data exist, better reporting of study procedures and standardization of the definition of abortion and abortion-related mortality should be encouraged.     

Hospital Door Handle Design and Their Contamination with Bacteria: A Real Life Observational Study. Are We Pulling against Closed Doors?

Objective

To determine whether microbial contamination of door handles in two busy intensive care units and one high dependency unit was related to their design, location, and usage.

Design

Observational study of the number of viable bacteria on existing door handles of different design at defined entry/exit points with simultaneous data collection of who used these doors and how often.

Setting

Two busy specialised intensive care units and one high dependency unit in a tertiary referral NHS neurological hospital.

Main outcome measures

Surface bacterial density on door handles with reference to design, location, and intensity of use.

Results

We found a significant correlation between the frequency of movements through a door and the degree to which it was contaminated (p = <0.01). We further found that the door''s location, design and mode of use all influenced contamination. When compared to push plate designs, pull handles revealed on average a five fold higher level of contamination; lever handles, however, displayed the highest levels of bacterial contamination when adjusted for frequency of use. We also observed differences in contamination levels at doors between clinical areas, particularly between the operating theatres and one of the ICUs.

Conclusions

Door handles in busy, “real life” high acuity clinical environments were variably contaminated with bacteria, and the number of bacteria found related to design, location, mode and frequency of operation. Largely ignored issues of handle and environmental design can support or undermine strategies designed to limit avoidable pathogen transmission, especially in locations designed to define “thresholds” and impose physical barriers to pathogen transmission between clinical areas. Developing a multidisciplinary approach beyond traditional boundaries for purposes of infection control may release hitherto unappreciated options and beneficial outcomes for the control of at least some hospital acquired infections.     

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

Background

Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.

Objectives

1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs.

Data sources

Pubmed and Science Citation Index.

Study eligibility criteria, participants, and interventions

Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a “new user” design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events.

Study appraisal and synthesis methods

For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference—comparing FGAs to SGAs—mediated by their difference in risk for the medical event.

Results

We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference.

Conclusions

The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.     

The Apgar Score and Infant Mortality

Objective

To evaluate if the Apgar score remains pertinent in contemporary practice after more than 50 years of wide use, and to assess the value of the Apgar score in predicting infant survival, expanding from the neonatal to the post-neonatal period.

Methods

The U.S. linked live birth and infant death dataset was used, which included 25,168,052 singleton births and 768,305 twin births. The outcome of interest was infant death within 1 year after birth. Cox proportional hazard-model was used to estimate risk ratio of infant mortality with different Apgar scores.

Results

Among births with a very low Apgar score at five minutes (1–3), the neonatal and post-neonatal mortality rates remained high until term (≥ 37 weeks). On the other hand, among births with a high Apgar score (≥7), neonatal and post-neonatal mortality rate decreased progressively with gestational age. Non-Hispanic White had a consistently higher neonatal mortality than non-Hispanic Black in both preterm and term births. However, for post-neonatal mortality, Black had significantly higher rate than White. The pattern of changes in neonatal and post-neonatal mortality by Apgar score in twin births is essentially the same as that in singleton births.

Conclusions

The Apgar score system has continuing value for predicting neonatal and post-neonatal adverse outcomes in term as well as preterm infants, and is applicable to twins and in various race/ethnic groups.     

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program – A Markov Model

Background

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.

Objective

To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.

Design

Markov decision model.

Data Sources

Published data.

Target Population

Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.

Time Horizon

The 5 years after initial evaluation for OSAS.

Perspective

Societal.

Interventions

Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.

Outcomes measures

Quality of life, survival and costs for each screening strategy.

Results of base-case analysis

Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.

Results of sensitivity analysis

Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.

Conclusions

CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.     

Maternal and Neonatal Mortality in South-West Ethiopia: Estimates and Socio-Economic Inequality

Introduction

Ethiopia has achieved the fourth Millennium Development Goal by reducing under 5 mortality. Nevertheless, there are challenges in reducing maternal and neonatal mortality. The aim of this study was to estimate maternal and neonatal mortality and the socio-economic inequalities of these mortalities in rural south-west Ethiopia.

Methods

We visited and enumerated all households but collected data from those that reported pregnancy and birth outcomes in the last five years in 15 of the 30 rural kebeles in Bonke woreda, Gamo Gofa, south-west Ethiopia. The primary outcomes were maternal and neonatal mortality and a secondary outcome was the rate of institutional delivery.

Results

We found 11,762 births in 6572 households; 11,536 live and 226 stillbirths. There were 49 maternal deaths; yielding a maternal mortality ratio of 425 per 100,000 live births (95% CI:318–556). The poorest households had greater MMR compared to richest (550 vs 239 per 100,000 live births). However, the socio-economic factors examined did not have statistically significant association with maternal mortality. There were 308 neonatal deaths; resulting in a neonatal mortality ratio of 27 per 1000 live births (95% CI: 24–30). Neonatal mortality was greater in households in the poorest quartile compared to the richest; adjusted OR (AOR): 2.62 (95% CI: 1.65–4.15), headed by illiterates compared to better educated; AOR: 3.54 (95% CI: 1.11–11.30), far from road (≥6 km) compared to within 5 km; AOR: 2.40 (95% CI: 1.56–3.69), that had three or more births in five years compared to two or less; AOR: 3.22 (95% CI: 2.45–4.22). Households with maternal mortality had an increased risk of stillbirths; OR: 11.6 (95% CI: 6.00–22.7), and neonatal deaths; OR: 7.2 (95% CI: 3.6–14.3). Institutional delivery was only 3.7%.

Conclusion

High mortality with socio-economic inequality and low institutional delivery highlight the importance of strengthening obstetric interventions in rural south-west Ethiopia.     

Frequency of Retinopathy of Prematurity in Premature Neonates with a Birth Weight below 1500 Grams and a Gestational Age Less than 32 Weeks: A Study from a Tertiary Care Hospital in a Lower-Middle Income Country…

Introduction

Retinopathy of prematurity (ROP) is a treatable cause of blindness in neonates. In Pakistan, ROP is often not recognized early because screening and treatment programs are not yet in place in most neonatal units, even in tertiary care hospitals. It is hoped that this report will help inform medical professionals of the magnitude of the problem and help to design appropriate management strategies.

Objectives

The aim was to determine the frequency of ROP in premature and very low birth weight (BW) neonates (BW<1500 g and gestational age (GA) <32 weeks).

Study Design

Cross-sectional study.

Study Setting

Neonatal intensive care unit (NICU) of a tertiary care hospital in Karachi, Pakistan.

Study Duration

From June 2009 to May 2010.

Subjects and Methods

Neonates with a Birth weight (BW) <1500 g and Gestational Age (GA) <32 weeks who were admitted to the NICU and received an eye examination, or were referred for a ROP eye examination as an outpatient, were included in the study. GA was estimated from intrauterine ultrasound findings. Neonates with major congenital malformations, syndromes or congenital cataracts or tumors of the eyes, and those that died before the eye examination or did not attend the out patients department for an eye examination, were excluded. The neonatal eye examination was performed by a trained ophthalmologist at 4 or 6 weeks of age.

Results

Out of 86 neonates, ROP was identified in nine neonates (10.5%) at the first eye examination. ROP was significantly associated with BW (P = 0.037), GA (P = 0.033), and chronological age (P<0.001).

Conclusions

we identified ROP in 10.5% of neonates at first eye examination. Significant associations between ROP and a GA<32 weeks and a BW<1500 g were also observed.we also stress that serial follow-up of neonates at risk for ROP is important when making a final diagnosis.     

Malaria Prevention with IPTp during Pregnancy Reduces Neonatal Mortality

Background

In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.

Methods

In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP.

Findings

There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024].

Conclusions

Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00209781","term_id":"NCT00209781"}}NCT00209781     

The Perspective of Rural Physicians Providing Abortion in Canada: Qualitative Findings of the BC Abortion Providers Survey (BCAPS)

Background

An increasing proportion of Canadian induced abortions are performed in large urban areas. For unknown reasons the number of rural abortion providers in Canadian provinces, such as British Columbia (BC), has declined substantially. This study explored the experiences of BC rural and urban physicians providing abortion services.

Methods

The mixed methods BC Abortion Providers Survey employed self-administered questionnaires, distributed to all known current and some past BC abortion providers in 2011. The optional semi-structured interviews are the focus of this analysis. Interview questions probed the experiences, facilitators and challenges faced by abortion providers, and their future intentions. Interviews were transcribed and analyzed using cross-case and thematic analysis.

Results

Twenty interviews were completed and transcribed, representing 13/27 (48.1%) rural abortion providers, and 7/19 (36.8%) of urban providers in BC. Emerging themes differed between urban and rural providers. Most urban providers worked within clinics and reported a supportive environment. Rural physicians, all providing surgical abortions within hospitals, reported challenging barriers to provision including operating room scheduling, anesthetist and nursing logistical issues, high demand for services, professional isolation, and scarcity of replacement abortion providers. Many rural providers identified a need to “fly under the radar” in their small community.

Discussion

This first study of experiences among rural and urban abortion providers in Canada identifies addressable challenges faced by rural physicians. Rural providers expressed a need for increased support from hospital administration and policy. Further challenges identified include a desire for continuing professional education opportunities, and for available replacement providers.     

Postoperative Hypoxia and Length of Intensive Care Unit Stay after Cardiac Surgery: The Underweight Paradox?

Objective

Cardiac operations with cardiopulmonary bypass can be associated with postoperative lung dysfunction. The present study investigates the incidence of postoperative hypoxia after cardiac surgery, its relationship with the length of intensive care unit stay, and the role of body mass index in determining postoperative hypoxia and intensive care unit length of stay.

Design

Single-center, retrospective study.

Setting

University Hospital. Patients. Adult patients (N = 5,023) who underwent cardiac surgery with CPB.

Interventions

None.

Measurements and main results

According to the body mass index, patients were attributed to six classes, and obesity was defined as a body mass index >30. POH was defined as a PaO2/FiO2 ratio <200 at the arrival in the intensive care unit. Postoperative hypoxia was detected in 1,536 patients (30.6%). Obesity was an independent risk factor for postoperative hypoxia (odds ratio 2.4, 95% confidence interval 2.05–2.78, P = 0.001) and postoperative hypoxia was a determinant of intensive care unit length of stay. There is a significant inverse correlation between body mass index and PaO2/FiO2 ratio, with the risk of postoperative hypoxia increasing by 1.7 folds per each incremental body mass index class. The relationship between body mass index and intensive care unit length of stay is U-shaped, with longer intensive care unit stay in underweight patients and moderate-morbid obese patients.

Conclusions

Obese patients are at higher risk for postoperative hypoxia, but this leads to a prolonged intensive care unit stay only for moderate-morbid obese patients. Obese patients are partially protected against the deleterious effects of hemodilution and transfusions. Underweight patients present the “paradox” of a better lung gas exchange but a longer intensive care unit stay. This is probably due to a higher severity of their cardiac disease.     

ThermoSpots to Detect Hypothermia in Children with Severe Acute Malnutrition

Introduction

Hypothermia is a risk factor for increased mortality in children with severe acute malnutrition (SAM). Yet frequent temperature measurement remains unfeasible in under-resourced units in developing countries. ThermoSpot is a continuous temperature monitoring sticker designed originally for neonates. When applied to skin, its liquid crystals are designed to turn black with hypothermia and remain green with normothermia.

Aims

To (i) estimate the diagnostic accuracy of ThermoSpots for detecting WHO-defined hypothermia (core temperature <35.5°C or peripheral temperature <35.0°C) in children with SAM and (ii) determine their acceptability amongst mothers.

Methods

Children with SAM in a malnutrition unit in Malawi were enrolled during March-July 2010. The sensitivity and specificity of ThermoSpots were calculated by comparing the device colour against ‘gold standard’ rectal temperatures taken on admission and follow up peripheral temperatures taken until discharge. Guardians completed a questionnaire to assess acceptability.

Results

Hypothermia was uncommon amongst the 162 children enrolled. ThermoSpot successfully detected the one rectal temperature and two peripheral temperatures recorded that met the WHO definition of hypothermia. Overall, 3/846 (0.35%) temperature measurements were in the WHO-defined hypothermia range. Interpreting the brown transition colour (between black and green) as hypothermia improved sensitivities. For milder hypothermia definitions, sensitivities declined (<35.4°C, 50.0%; <35.9°C, 39.2%). Specificity was consistently above 94%. From questionnaires, 40/43 (93%) mothers reported they were 90–100% happy with the device overall. Free-text answers revealed themes of “Skin Rashes”, “User-satisfaction” and “Empowerment".

Conclusion

Although hypothermia was uncommon in this study, ThermoSpots successfully detected these episodes in malnourished children and were acceptable to mothers. Research in settings where hypothermia is common is needed to determine performance with certainty. Instructing users to act when the device’s transition colour appears could improve accuracy. If reliable, ThermoSpots may offer simple, acceptable and continuous temperature measurement for high-burden areas and reduce the workload of over-stretched staff.     

Cancer Mortality in Chinese Chrysotile Asbestos Miners: Exposure-Response Relationships

Objective

This study was conducted to assess the relationship of mortality from lung cancer and other selected causes to asbestos exposure levels.

Methods

A cohort of 1539 male workers from a chrysotile mine in China was followed for 26 years. Data on vital status, occupation and smoking were collected from the mine records and individual contacts. Causes and dates of death were further verified from the local death registry. Individual cumulative fibre exposures (f-yr/ml) were estimated based on converted dust measurements and working years at specific workshops. Standardized mortality ratios (SMRs) for lung cancer, gastrointestinal (GI) cancer, all cancers and nonmalignant respiratory diseases (NMRD) stratified by employment years, estimated cumulative fibre exposures, and smoking, were calculated. Poisson models were fitted to determine exposure-response relationships between estimated fibre exposures and cause-specific mortality, adjusting for age and smoking.

Results

SMRs for lung cancer increased with employment years at entry to the study, by 3.5-fold in ≥10 years and 5.3-fold in ≥20 years compared with <10 years. A similar trend was seen for NMRD. Smokers had greater mortality from all causes than nonsmokers, but the latter also had slightly increased SMR for lung cancer. No excess lung cancer mortality was observed in cumulative exposures of <20 f-yrs/ml. However, significantly increased mortality was observed in smokers at the levels of ≥20 f-yrs/ml and above, and in nonsmokers at ≥100 f-yrs/ml and above. A similarly clear gradient was also displayed for NMRD. The exposure-response relationships with lung cancer and NMRD persisted in multivariate analysis. Moreover, a clear gradient was shown in GI cancer mortality when age and smoking were adjusted for.

Conclusion

There were clear exposure-response relationships in this cohort, which imply a causal link between chrysotile asbestos exposure and lung cancer and nonmalignant respiratory diseases, and possibly to gastrointestinal cancer, at least for smokers.     

The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study

Background

Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980–2004.

Methods and Findings

There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is “prolonged,” suggesting this condition remains a significant contributor to perinatal mortality and morbidity.

Conclusions

In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing. Please see later in the article for the Editors'' Summary     

Utilization of Inhaled Corticosteroids for Infants with Bronchopulmonary Dysplasia

Objective

To determine demographic and clinical variables associated with inhaled corticosteroid administration and to evaluate between-hospital variation in inhaled steroid use for infants with bronchopulmonary dysplasia (BPD).

Design

Retrospective Cohort Study.

Setting

Neonatal units of 35 US children''s hospitals; as recorded in the Pediatric Health Information System (PHIS) database.

Patients

1429 infants with evolving BPD at 28 days who were born at <29 weeks gestation with birth weight <1500 grams, admitted within the first 7 postnatal days, and discharged between January 2007–June 2011.

Results

Inhaled steroids were prescribed to 25% (n = 352) of the cohort with use steadily increasing during the first two months of hospitalization. The most frequently prescribed steroid was beclomethasone (n = 194, 14%), followed by budesonide (n = 125, 9%), and then fluticasone (n = 90, 6%). Birth gestation <24 weeks, birth weight 500–999 grams, and prolonged ventilation all increased the adjusted odds of ever receiving inhaled corticosteroids (p<0.05). Wide variations between hospitals in the frequency of infants ever receiving inhaled steroids (range: 0–60%) and the specific drug prescribed were noted. This variation persisted, even after controlling for observed confounders.

Conclusions

Inhaled corticosteroid administration to infants with BPD is common in neonatal units within U.S. Children''s hospitals. However, its utilization varies markedly between centers from no treatment at some institutions to the majority of infants with BPD being treated at others. This supports the need for further research to identify the benefits and potential risks of inhaled steroid usage in infants with BPD.     

Culture of Airway Epithelial Cells from Neonates Sampled within 48-Hours of Birth

Introduction

Little is known about how neonatal airway epithelial cell phenotype impacts on respiratory disease in later life. This study aimed to establish a methodology to culture and characterise neonatal nasal epithelial cells sampled from healthy, non-sedated infants within 48 hours of delivery.

Methods

Nasal epithelial cells were sampled by brushing both nostrils with an interdental brush, grown to confluence and sub-cultured. Cultured cells were characterised morphologically by light and electron microscopy and by immunocytochemistry. As an exemplar pro-inflammatory chemokine, IL-8 concentrations were measured in supernatants from unstimulated monolayers and after exposure to IL-1β/TNF-α or house dust mite extract.

Results

Primary cultures were successfully established in 135 (91%) of 149 neonatal samples seeded, with 79% (n  =  117) successfully cultured to passage 3. The epithelial lineage of the cells was confirmed by morphological analysis and immunostaining. Constitutive IL-8 secretion was observed and was upregulated by IL-1β/TNF-α or house dust mite extract in a dose dependent manner.

Conclusion

We describe a safe, minimally invasive method of culturing nasal epithelial cells from neonates suitable for functional cell analysis offering an opportunity to study “naïve” cells that may prove useful in elucidating the role of the epithelium in the early origins of asthma and/or allergic rhinitis.