Maternal pesticides exposure in pregnancy and the risk of wheezing in infancy: A prospective cohort study.

INTRODUCTION: Pesticide exposure in pregnancy may have health effects in the offspring. We studied whether maternal pesticides exposure during pregnancy is associated with infant wheezing. METHODS: The study involved 5997 children from the Italian NINFEA birth cohort, whose mothers were recruited during pregnancy between 2005 and 2016. We used questionnaires completed during pregnancy and 6 months after delivery to derive the following indirect measures of exposure: i) Self-reported pesticide use during the first and the third trimester of pregnancy; (ii) Agricultural activities during the same trimesters. We also evaluated the exposure to agricultural pesticides applied near home using the Corine Land Cover inventory to derive the proportion of a 200-metre buffer area around maternal home address covered by agricultural crops and specific crop types (arable land, fruit trees, heterogeneous cultivations). Questionnaires completed when the child turned 18 months reported information on wheezing between 6 and 18 months of age. We estimated the odds ratios of wheezing adjusting for the following maternal characteristics: age, education, parity, asthma, atopy, smoking in pregnancy, region and area of residence, pet ownership during pregnancy. Crops proximity analyses were restricted to residents in rural areas (N = 1674). RESULTS: Agricultural activities during pregnancy were not associated with infant wheezing. Compared to no pesticide use, there was a weak positive association for self-reported use in the third trimester (POR: 1.30; 95 %CI 0.95-1.78) and a stronger association for use in both trimesters (POR: 1.72; 95 %CI 1.11-2.65). The relationship between the proportion of crops around the home address and the risk of infant wheezing, was J-shaped, in particular for fruit trees with the lowest risk for mid values and elevated risk for higher values. CONCLUSION: We found some evidence of association for maternal pesticide use in pregnancy and residential proximity to fruit trees cultivations with infant wheezing.

Five-minute Apgar score and outcomes in neonates of 24-28 weeks' gestation.

OBJECTIVES: To assess associations between 5 min Apgar score and mortality and severe neurological injury (SNI) and to report test characteristics in preterm neonates. DESIGN, SETTING AND PATIENTS: Retrospective cohort study of neonates 240 to 286 weeks' gestation born between 2007 and 2016 and admitted to neonatal units in 11 high-income countries. EXPOSURE: 5 min Apgar score. MAIN OUTCOME MEASURES: In-hospital mortality and SNI defined as grade 3 or 4 periventricular/intraventricular haemorrhage or periventricular leukomalacia. Outcome rates were calculated for each Apgar score and compared after adjustment. The diagnostic characteristics and ORs for each value from 0 versus 1-10 to 0-9 versus 10, with 1-point increments were calculated. RESULTS: Among 92 412 included neonates, as 5 min Apgar score increased from 0 to 10, mortality decreased from 60% to 8%. However, no clear increasing or decreasing pattern was identified for SNI. There was an increase in sensitivity and decrease in specificity for both mortality and SNI associated with increasing scores. The Apgar score alone had an area under the curve of 0.64 for predicting mortality, which increased to 0.73 with the addition of gestational age. CONCLUSIONS: In neonates of 24-28 weeks' gestation admitted to neonatal units, higher 5 min Apgar score was associated with lower mortality in a graded manner, while the association with SNI remained relatively constant at all scores. Among survivors, low Apgar scores did not predict SNI.

Modifiable environmental factors predispose term infants to bronchiolitis but bronchiolitis itself predisposes to respiratory sequelae.

INTRODUCTION: Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections. AIM: The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalization for bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort, who never had bronchiolitis. METHODS: We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma. RESULTS: Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]: 0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthma by 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test. CONCLUSION: Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma.

COVID-19-like symptoms and their relation to the SARS-CoV-2 epidemic in children and adults of an Italian birth cohort

OBJECTIVES: to estimate the population prevalence of COVID-19-like symptoms in children and adults during the first SARS-CoV-2 epidemic wave hitting Italy in the spring 2020; to assess their geographical correlation with the cumulative number of COVID-19 cases by province; to analyse their clustering within families; to estimate their sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for COVID-19 diagnosis in individuals tested for SARS-CoV-2. DESIGN: cross-sectional study nested within a birth cohort. SETTING AND PARTICIPANTS: mothers participating in an Italian birth cohort (NINFEA) were invited to complete an online questionnaire on COVID-19-like symptoms in their household. MAIN OUTCOME MEASURES: population prevalence of COVID-19-like symptoms in children and adults, geographical correlation of COVID-19-like symptoms with the cumulative number of COVID-19 cases by province, clustering of COVID-19-like symptoms within families, and sensitivity, PPV and NPV of COVID-19-like symptoms for COVID-19 diagnosis in individuals tested for SARS-CoV-2. RESULTS: information was collected on 3,184 households, 6,133 adults, and 5,751 children. In the period March-April 2020, 55.4% of the NINFEA families had at least one member with at least one COVID-19-like symptom. There was a strong geographical correlation between the population cumulative incidence of COVID-19 and the prevalence of muscle pain, fatigue, low-grade fever, and breathing difficulties in adults (Spearman's rho >=0.70). Having at least one family member with a COVID-19 diagnosis, compared with none tested for SARS-CoV-2, was associated with an increased prevalence ratio (PR) of almost all COVID-19-like symptoms in adults, and only of low-grade fever (37-37.5°C; PR 4.54; 95%CI 2.20-9.40) and anosmia/dysgeusia in children. Among adults with COVID-19 diagnosis, fatigue, muscle pain, and fever had a sensitivity >=70%. In individuals tested for SARS-CoV-2, with a 16.6% prevalence of COVID-19, breathing difficulties and nausea/vomiting had the highest PPVs, with point estimates close to 60%, and with NPVs close to 90%. CONCLUSIONS: the geographical prevalence of COVID-19-like symptoms in adults may inform on local disease clusters, while certain symptoms in family members of confirmed COVID-19 cases could help identify the intra-familial spread of the virus and its further propagation in the community. Low-grade fever is frequent in children with at least one household member with COVID-19 and possibly indicates child infection.

Inter-center variability in neonatal outcomes of preterm infants: A longitudinal evaluation of 298 neonatal units in 11 countries.

Collaboration and cooperation of clinicians and neonatal units at regional, national, and international levels are key features of many networks or systems that aim to improve neonatal outcomes. Network performance is typically assessed by comparing individual, unit-level outcomes. In this paper, we provide insight into another dimension, i.e., inter-center outcome variation in 10 national/regional neonatal collaborations from 11 high-income countries. We illustrate the use of coefficients of variation for evaluation of mortality and a composite outcome of mortality, severe neurological injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia, as a measure of inter-center variation. These inter-center variation estimates could help to identify areas of opportunities and challenges for each country/region; they also provide "macro"-level evaluations that can be useful for clinicians, administrators, managers and policy makers.

Neonatal outcomes of extremely preterm twins by sex pairing: an international cohort study.

OBJECTIVE: Infant boys have worse outcomes than girls. In twins, the 'male disadvantage' has been reported to extend to female co-twins via a 'masculinising' effect. We studied the association between sex pairing and neonatal outcomes in extremely preterm twins. DESIGN: Retrospective cohort study SETTING: Eleven countries participating in the International Network for Evaluating Outcomes of Neonates. PATIENTS: Liveborn twins admitted at 23-29 weeks' gestation in 2007-2015. MAIN OUTCOME MEASURES: We examined in-hospital mortality, grades 3/4 intraventricular haemorrhage or cystic periventricular leukomalacia (IVH/PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment and a composite outcome (mortality or any of the outcomes above). RESULTS: Among 20 924 twins, 38% were from male-male pairs, 32% were from female-female pairs and 30% were sex discordant. We had no information on chorionicity. Girls with a male co-twin had lower odds of mortality, IVH/PVL and the composite outcome than girl-girl pairs (reference group): adjusted OR (aOR) (95% CI) 0.79 (0.68 to 0.92), 0.83 (0.72 to 0.96) and 0.88 (0.79 to 0.98), respectively. Boys with a female co-twin also had lower odds of mortality: aOR 0.86 (0.74 to 0.99). Boys from male-male pairs had highest odds of BPD and composite outcome: aOR 1.38 (1.24 to 1.52) and 1.27 (1.16 to 1.39), respectively. CONCLUSIONS: Sex-related disparities in outcomes exist in extremely preterm twins, with girls having lower risks than boys and opposite-sex pairs having lower risks than same-sex pairs. Our results may help clinicians in assessing risk in this large segment of extremely preterm infants.

Neonatal Outcomes in Very Preterm Infants With Severe Congenital Heart Defects: An International Cohort Study.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects (CHDs) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007-2015 at 24 to 31 weeks' gestation with birth weights <1500 g. Severe CHDs were defined by International Classification of Diseases, Ninth Revision (ICD-9) and Tenth (ICD-10) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in-hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score-matched odds ratios (ORs) were calculated. Analyses were stratified by type of CHD, gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score-matched OR, 2.30; 95% CI, 1.61-3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score-matched OR (4.96; 95% CI, 2.11-11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at <27 weeks' gestational age, adjusted OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76-20.70) at 31 weeks' gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries.

OBJECTIVE: To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. STUDY DESIGN: In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 240/7 to 316/7 weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. RESULTS: For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. CONCLUSIONS: In most countries, mortality decreased whereas BPD increased for neonates born very preterm.

A Panel Study on Lung Function and Bronchial Inflammation among Children Exposed to Ambient SO2 from an Oil Refinery.

To determine the acute effects on respiratory function of children exposed to sulphur dioxide (SO2), we conducted two population-based longitudinal investigations near a major oil refinery. We enrolled 233 children, age 8⁻14, in Sarroch (Italy). The first study entailed five monthly spirometric visits (Panel 5). In a subgroup, children positive for history of respiratory symptoms were tested weekly (20 times) with spirometry and fractional exhaled nitric oxide (FeNO) measurement (Panel 20). Baseline questionnaires and daily diaries were recorded. SO2, NO2, PM10 and O3 were measured by monitoring stations. Multiple regression models were fitted. Using a multipollutant model, we found that a 10 µg/m³ SO2 increase at lag0⁻2 days determined a percent variation (PV) of -3.37 (90% confidence interval, CI: -5.39; -1.30) for forced expiratory volume after one second (FEV1) in Panel 5 and a PV = -3.51 (90% CI: -4.77; -2.23) in Panel 20. We found a strong dose-response relation: 1-h SO2 peaks >200 µg/m³ at lag2 days = FEV1 PV -2.49. For FeNO, we found a PV = 38.12 (90% CI: 12.88; 69.01) for each 10 µg/m³ SO2 increase at 8-h time lag and a strong dose-response relation. Exposure to SO2 is strongly associated with reduction of lung function and an increase in airway inflammation. This new evidence of harmful effects of SO2 peaks should induce regulatory intervention.

Neonatal Outcomes of Very Preterm or Very Low Birth Weight Triplets.

OBJECTIVES: To compare the neonatal outcomes of very preterm triplets with those of matched singletons using a large international cohort. METHODS: A retrospective matched-cohort study of preterm triplets and singletons born between 2007 and 2013 in the International Network for Evaluation of Outcomes in neonates database countries and matched by gestational age, sex, and country of birth was conducted. The primary outcome was a composite of mortality or severe neonatal morbidity (severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia). Unadjusted and adjusted odds ratios with 95% confidence intervals (CIs) were calculated for model 1 (maternal hypertension and birth weight z score) and model 2 (variables in model 1, antenatal steroids, and mode of birth). Models were fitted with generalizing estimating equations and random effects modeling to account for clustering. RESULTS: A total of 6079 triplets of 24 to 32 weeks' gestation or 500 to 1499 g birth weight and 18 232 matched singletons were included. There was no difference in the primary outcome between triplets and singletons (23.4% vs 24.0%, adjusted odds ratio: 0.91, 95% CI: 0.83-1.01 for model 1 and 1.00, 95% CI: 0.90-1.11 for model 2). Rates of severe neonatal morbidities did not differ significantly between triplets and singletons. The results were also similar for a subsample of the cohort (1648 triplets and 4944 matched singletons) born at 24 to 28 weeks' gestation. CONCLUSIONS: No significant differences were identified in mortality or major neonatal morbidities between triplets who were very low birth weight or very preterm and matched singletons.

Lung function in a cohort of 5-year-old children born very preterm.

OBJECTIVE: We assessed lung function and respiratory health in an area-based prospective cohort of preschool children born very preterm. DESIGN: Lung function was measured by interrupter respiratory resistance (Rint) and forced oscillation technique (FOT) (respiratory resistance (Rrs8), reactance (Xrs8), and area under the reactance curve (AX)) at a median age of 5.2 years in a cohort of 194 children born at 22-31 weeks of gestational age (GA) in Tuscany, Italy. Respiratory symptoms and hospitalizations were also assessed. RESULTS: Mean (SD) lung function Z-scores were impaired in preterm children for Rint (0.72 (1.13)), Xrs8 (-0.28 (1.34)), and AX (0.29 (1.41)). However, only a relatively small proportion of children (14.5-17.4%) had values beyond the 95th centile or below the 5th. Children with bronchopulmonary dysplasia (BPD) (n = 24) had slightly but not significantly impaired lung function indices in comparison with those without BPD (n = 170). In a multivariable analysis, lower GA was associated with worse lung function indices. Fifty-five percent of children had a history of wheezing ever and 21% had been hospitalized in their lifetime because of lower respiratory infections; 31% had wheezing in the last 12 months and this was associated with increased Rrs8 (P = 0.04) and AX (P = 0.08), and with decreased Xrs8 (P = 0.04) Z-scores. CONCLUSIONS: Irrespectively of BPD preschool children born very preterm had impaired lung function indices, as measured by Rint and FOT, and a slightly higher burden of respiratory problems than the general population. GA seems to be crucial for lung development.

Association of Maternal Diabetes With Neonatal Outcomes of Very Preterm and Very Low-Birth-Weight Infants: An International Cohort Study.

Importance: Diabetes in pregnancy is associated with a 2-times to 3-times higher rate of very preterm birth than in women without diabetes. Very preterm infants are at high risk of death and severe morbidity. The association of maternal diabetes with these risks is unclear. Objective: To determine the associations between maternal diabetes and in-hospital mortality, as well as neonatal morbidity in very preterm infants with a birth weight of less than 1500 g. Design, Setting, Participants: This retrospective cohort study was conducted at 7 national networks in high-income countries that are part of the International Neonatal Network for Evaluating Outcomes in Neonates and used prospectively collected data on 76 360 very preterm, singleton infants without malformations born between January 1, 2007, and December 31, 2015, at 24 to 31 weeks' gestation with birth weights of less than 1500 g, 3280 (4.3%) of whom were born to diabetic mothers. Exposures: Any type of diabetes during pregnancy. Main Outcomes and Measures: The primary outcome was in-hospital mortality. The secondary outcomes were severe neonatal morbidities, including intraventricular hemorrhages of grade 3 to 4, cystic periventricular leukomalacia, retinopathy of prematurity needing treatment and bronchopulmonary dysplasia, and other morbidities, including respiratory distress, treated patent ductus arteriosus, and necrotizing enterocolitis. Odds ratios (ORs) with 95% confidence intervals were estimated, adjusted for potential confounders, and stratified by gestational age (GA), sex, and network. Results: The mean (SD) birth weight of offspring born to mothers with diabetes was significantly higher at 1081 (262) g than in offspring born to mothers without diabetes (mean [SD] birth weight, 1027 [270] g). Mothers with diabetes were older and had more hypertensive disorders, antenatal steroid treatments, and deliveries by cesarean delivery than mothers without diabetes. Infants of mothers with diabetes were born at a later GA than infants of mothers without diabetes. In-hospital mortality (6.6% vs 8.3%) and the composite of mortality and severe morbidity (31.6% vs 40.6%) were lower in infants of mothers with diabetes. However, in adjusted analyses, no significant differences in in-hospital mortality (adjusted OR, 1.16 (95% CI, 0.97-1.39) or the composite of mortality and severe morbidity (adjusted OR, 0.99 (95% CI, 0.88-1.10) were observed. With few exceptions, outcomes of infants born to mothers with and without diabetes were similar regardless of infant sex, GA, or country of birth. Conclusions and Relevance: In high-resource settings, maternal diabetes is not associated with an increased risk of in-hospital mortality or severe morbidity in very preterm infants with a birth weight of fewer than 1500 g.

Severe Paediatric Asthma Collaborative in Europe (SPACE): protocol for a European registry.

The development of new asthma biologics and receptor blockers for the treatment of paediatric severe asthma raises challenges. It is unclear whether there are sufficient children in Europe to recruit into randomised placebo-controlled trials to establish efficacy and safety in this age group. In February 2016, the European Respiratory Society funded a clinical research collaboration entitled "Severe Paediatric Asthma Collaborative in Europe" (SPACE). We now report the SPACE protocol for a prospective pan-European observational study of paediatric severe asthma. Inclusion criteria are: 1) age 6-17 years, 2) severe asthma managed at a specialised centre for ≥6 months, 3)clinical and spirometry evidence of asthma, and 4) reaching a pre-defined treatment threshold. The exclusion criterion is the presence of conditions which mimic asthma symptoms. Eligible children will be prospectively recruited into a registry, recording demographics, comorbidities, quality of life, family history, neonatal history, smoking history, asthma background, investigations, and treatment. Follow-up will provide longitudinal data on asthma control and treatment changes. The SPACE registry, by identifying well-phenotyped children eligible for clinical trials, and the amount of overlap in eligibility criteria, will inform the design of European trials in paediatric severe asthma, and facilitate observational research where data from single centres are limited.

[Communicating data of the Italian NINFEA birth cohort]. / Comunicare i dati della coorte italiana di nuovi nati NINFEA.

"In March 2016, the website of the NINFEA project (an Internet-based cohort set up to investigate the effects of exposures acting early in life) was enriched with the section «Data¼, which reports aggregated data for selected variables of the cohort. This article discusses the rationale for this new section, available data and their possible uses are described, and some results are compared with figures accessible from surveillance studies. The Italian birth cohort NINFEA includes 7,500 pregnant women, recruited through the Internet from 2005 to June 2016, and of their children, followed up with repeated questionnaires. Thus, the «Data¼ section is based on a selected population. Currently, this new section includes information on maternal lifestyles/characteristics in pregnancy (e.g., alcohol, smoking, use of medications), child health (e.g., obesity, asthma symptoms, growth) and behaviours (e.g., sleeping patterns, being breastfed). Up to December 18th, 2017, its pages were visited 12,620 times. Prevalences for selected variables (e.g., prepregnancy body mass index, breast feeding, infant sleeping position) are similar to those reported by surveillance studies. Aggregated exposure and outcome data from large cohorts can be systematically made publicly available. These data may be of interest to the participants, to population subgroups whose characteristics are similar to the study participants, and to researchers and policy makers, whenever similar data are not available from population-based surveillance systems."

The role of maternal anorexia nervosa and bulimia nervosa before and during pregnancy in early childhood wheezing: Findings from the NINFEA birth cohort study.

OBJECTIVE: This study evaluates associations of maternal eating disorders (bulimia nervosa, anorexia nervosa, and purging behaviors) with infant wheezing and examines the effects of eating disorders on several wheezing determinants. METHOD: We studied 5,150 singletons from the NINFEA birth cohort. Maternal bulimia nervosa and anorexia nervosa diagnoses were ascertained from the questionnaires completed in pregnancy and 6 months after delivery, and were analyzed as: ever diagnosis, only before pregnancy, and during pregnancy. Purging behaviors were assessed for 12 months before or during pregnancy. The associations with wheezing between 6 and 18 months of age were assessed in models adjusted for a priori selected confounders. RESULTS: Children born to mothers with lifetime eating disorders were at an increased risk of developing wheezing (adjusted OR 1.68; [95% CI: 1.08, 2.60]), and this risk further increased when the disorders were active during pregnancy (2.52 [1.23, 5.19]). Increased risk of offspring wheezing was observed also for purging behaviors without history of eating disorder diagnosis (1.50 [1.10, 2.04]). The observed associations were not explained by comorbid depression and/or anxiety. Bulimia nervosa and/or anorexia nervosa during pregnancy were also associated with several risk factors for wheezing, including maternal smoking, adverse pregnancy outcomes, shorter breastfeeding duration, and day-care attendance. DISCUSSION: The associations of maternal eating disorders with offspring wheezing suggest long-term adverse respiratory outcomes in children of mothers with eating disorders. A better understanding of mechanisms implicated is necessary to help reduce the respiratory disease burden in these children.

International variations and trends in the treatment for retinopathy of prematurity.

OBJECTIVE: To compare the rates of retinopathy of prematurity (ROP) and treatment of ROP by laser or intravitreal anti-vascular endothelial growth factor among preterm neonates from high-income countries participating in the International Network for Evaluating Outcomes (iNeo) of neonates. METHODS: A retrospective cohort study was conducted on extremely preterm infants weighing <1500 g at 240 to 276 weeks' gestation who were admitted to neonatal units in Australia/New Zealand, Canada, Finland, Israel, Japan, Spain, Sweden, Switzerland, Tuscany (Italy) and the UK between 2007 and 2013. Pairwise comparisons of ROP treatment in survivors between countries were evaluated by Poisson and multivariable logistic regression analyses after adjustment for confounders. A composite outcome of death or ROP treatment was compared between countries using logistic regression and standardised ratios. RESULTS: Of 48 087 infants included in the analysis, 81.8% survived to 32 weeks postmenstrual age, and 95% of survivors were screened for ROP. Rates of any ROP ranged from 25.2% to 91.0% in Switzerland and Japan, respectively, among those examined. The overall rate of those receiving treatment was 24.9%, which varied from 4.3% to 30.4%. Adjusted risk ratios for ROP treatment were lower for Switzerland in all pairwise comparisons, whereas Japan displayed significantly higher ratios. Comparisons of the composite outcome between countries revealed similar, but less marked differences. CONCLUSIONS: Rates of any ROP and ROP treatment varied significantly between iNeo members, while an overall decline in ROP treatment was observed during the study period. It is unclear whether these variations represent differences in care practices, diagnosis and/or treatment thresholds.

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.

Key paediatric messages from Amsterdam.

The Paediatric Assembly of the European Respiratory Society (ERS) maintained its high profile at the 2015 ERS International Congress in Amsterdam. There were symposia on preschool wheeze, respiratory sounds and cystic fibrosis; an educational skills workshop on paediatric respiratory resuscitation; a hot topic session on risk factors and early origins of respiratory diseases; a meet the expert session on paediatric lung function test reference values; and the annual paediatric grand round. In this report the Chairs of the Paediatric Assembly's Groups highlight the key messages from the abstracts presented at the Congress.

Occupational Exposure to Endocrine-Disrupting Chemicals and Birth Weight and Length of Gestation: A European Meta-Analysis.

BACKGROUND: Women of reproductive age can be exposed to endocrine-disrupting chemicals (EDCs) at work, and exposure to EDCs in pregnancy may affect fetal growth. OBJECTIVES: We assessed whether maternal occupational exposure to EDCs during pregnancy as classified by application of a job exposure matrix was associated with birth weight, term low birth weight (LBW), length of gestation, and preterm delivery. METHODS: Using individual participant data from 133,957 mother-child pairs in 13 European cohorts spanning births from 1994 through 2011, we linked maternal job titles with exposure to 10 EDC groups as assessed through a job exposure matrix. For each group, we combined the two levels of exposure categories (possible and probable) and compared birth outcomes with the unexposed group (exposure unlikely). We performed meta-analyses of cohort-specific estimates. RESULTS: Eleven percent of pregnant women were classified as exposed to EDCs at work during pregnancy, based on job title. Classification of exposure to one or more EDC group was associated with an increased risk of term LBW [odds ratio (OR) = 1.25; 95% CI: 1.04, 1.49], as were most specific EDC groups; this association was consistent across cohorts. Further, the risk increased with increasing number of EDC groups (OR = 2.11; 95% CI: 1.10, 4.06 for exposure to four or more EDC groups). There were few associations (p < 0.05) with the other outcomes; women holding job titles classified as exposed to bisphenol A or brominated flame retardants were at higher risk for longer length of gestation. CONCLUSION: Results from our large population-based birth cohort design indicate that employment during pregnancy in occupations classified as possibly or probably exposed to EDCs was associated with an increased risk of term LBW. Citation: Birks L, Casas M, Garcia AM, Alexander J, Barros H, Bergström A, Bonde JP, Burdorf A, Costet N, Danileviciute A, Eggesbø M, Fernández MF, González-Galarzo MC, Grazuleviciene R, Hanke W, Jaddoe V, Kogevinas M, Kull I, Lertxundi A, Melaki V, Andersen AM, Olea N, Polanska K, Rusconi F, Santa-Marina L, Santos AC, Vrijkotte T, Zugna D, Nieuwenhuijsen M, Cordier S, Vrijheid M. 2016. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: a European meta-analysis. Environ Health Perspect 124:1785-1793; http://dx.doi.org/10.1289/EHP208.

Exploring educational disparities in risk of preterm delivery: a comparative study of 12 European birth cohorts.

BACKGROUND: An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. METHODS: The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). RESULTS: Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. CONCLUSIONS: Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.