Maternal antenatal mental health and its associations with perinatal outcomes and the use of healthcare services in children from the NINFEA birth cohort study.

To investigate the associations between maternal mental health disorders before and during pregnancy and perinatal outcomes and child healthcare utilization between 6 and 18 months of age. Among the 6814 mother-child pairs from the Italian Internet-based NINFEA birth cohort, maternal depression, anxiety, and sleep disorders diagnosed by a physician before and during pregnancy were assessed through self-reported questionnaires completed during pregnancy and 6 months after delivery. Perinatal outcomes (preterm birth, birth weight, small for gestational age, congenital anomalies, and neonatal intensive care unit (NICU)) and children's healthcare utilization (emergency department (ED) visits, hospitalizations, and outpatient visits) were reported by mothers at 6 and 18 months postpartum. We used regression models adjusted for maternal age, education, parity, country of birth, region of delivery, and household income. Maternal mental health disorders were not associated with perinatal outcomes, except for depression, which increased the risk of offspring admission to NICU, and anxiety disorders during pregnancy, which were associated with preterm birth and lower birth weight. Children born to mothers with depression/anxiety disorders before pregnancy, compared to children of mothers without these disorders, had an increased odds of a visit to ED for any reason (odds ratio (ORadj) = 1.26, 95% confidence interval (CI): 1.02-1.54), of an ED visit resulting in hospitalization (ORadj = 1.75, 95%CI: 1.27-2.42), and of planned hospital admissions (ORadj = 1.55, 95%CI: 1.01-2.40). These associations with healthcare utilization were similar for mental disorders also during pregnancy. The association pattern of maternal sleep disorders with perinatal outcomes and child healthcare utilization resembled that of maternal depression and/or anxiety disorders with these outcomes.   Conclusion: Antenatal maternal mental health is a potential risk factor for child-health outcomes and healthcare use. Early maternal mental health interventions may help to promote child health and reduce healthcare costs. What is Known: • Poor maternal mental health affects pregnancy outcomes and child health, and children of mothers with mental health conditions tend to have increased healtcare utilization. • Parents with poor mental health often face challenges in caring for their children and have less parenting self-efficacy, which could potentially lead to frequent medical consultations for minor health issues. What is New: • Maternal pre-pregnancy mental disorders were not associated with preterm birth, low birth weight, SGA, and congenital anomalies, except for depression, which increased the risk of offspring admission to NICU. Anxiety disorders during pregnancy were associated with lower birth weight and an increased odds of preterm birth. • Maternal depression and/or anxiety and sleep disorders, both before and during pregnancy, were associated with an increase in children's healthcare utilization between 6 and 18 months of life.

Examining the relationship between the environmental impact of diet and child growth from a co-benefit perspective.

The adoption of diets that minimize both their environmental impacts and weight excess in children would be a major co-benefit for climate change mitigation. We evaluated the relationship between child diet-related environmental impact and anthropometric characteristics in an Italian birth cohort. The study involved 2127 children of the Piccolipiù birth cohort. At 4 years, their diet in the previous two months was assessed through a questionnaire, from which we derived individual: (i) diet-related daily greenhouse gas emissions (GHGE), (ii) land use (LU), (iii) adherence to the Mediterranean Diet (MD) and (iv) red meat consumption. We related these variables with overweight and obesity, waist circumference, and height at 4 years using regression models adjusted for a priori selected confounders. Diet-related GHGE and LU had a positive weak association with overweight and obesity, with an odds ratio (OR) for the fourth vs. second quartile of 1.30 for both GHGE (95% confidence intervals -CI-: 0.96; 1.77) and LU (95% CI: 0.96-1.76). Both OR estimates increased after adjustment for energy intake. GHGE and LU were not associated with height, with the exception of shorter children in the first quartile. A high vs. low MD adherence was associated with an increase in height Z-score of 0.11 (95% CI 0.01; 0.21). No association was found for red meat consumption. These results suggest that lowering the impact of high environmental impact diets may have, if anything, beneficial effects on child obesity, overweight, and height, with pro-MD patterns playing an important role.

Breastfeeding and presence of the companion of woman's choice during COVID-19 pandemic in Italy: regional population-based routine data and best practices at birth

OBJECTIVES: to describe the monthly trend of breastfeeding during hospitalization and the presence of companion of woman's choice during labour and birth, and the key regional responders' perspective of homogeneity/heterogeneity of the presence of the support person, before, during (February-May 2020), and after the first COVID-19 pandemic wave in a few Italian Regions. DESIGN: two-phase study. SETTING AND PARTICIPANTS: data from the italian birth certificate of six Italian Regions between 01.01.2019 and 31.03.2021 were analysed. Semi-structured interviews were conducted with the key regional respondents. MAIN OUTCOME MEASURES: the frequency distributions of breastfeeding and the presence of companion of woman's choice were calculated as a whole and for each Region. RESULTS: the infant feeding practices experienced smaller changes during COVID-19 pandemic than the presence of the companion of woman's choice during labour and birth, from January 2019 to March 2021. The highest value of exclusive breastfeeding was recorded in September 2020 (72.1%; 95%CI 71.3-72.8) in all Regions, while the lowest was recorded in March 2021 (62.5%; 95%CI 61.5-63.4). The presence of companion of woman's choice during labour and birth decreased during the pandemic and did not return to pre-pandemic levels. The highest value of presence of father during birth was recorded in March 2019 (59.0%; 95%CI 58.2-59.8), while the lowest in April 2020 (50.0%; 95%CI 49.1-50.8). The main emerging themes were: the existence of national, regional and local indications; the facilitators (e.g., Baby-Friendly Hospital Initiative implementation, strong motivation of the staff) and the critical points (e.g., inadequate analysis of the clinical-epidemiological context, inhomogeneous indications) of management of the support person presence. CONCLUSIONS: the emergency has changed the provision of health services that not always guaranteed the application of best practices. It would be desirable to work for assessing the appropriateness of the birth certificate data to collect more accurate information and to provide clinical recommendations.

Family socioeconomic position and changes in planned health care for children with chronic diseases during the COVID-19 pandemic in Italy.

Introduction: In this study, we aimed at evaluating whether, during the COVID-19 pandemic, children affected by chronic diseases were impacted by the deferral of planned healthcare caused by the restriction measures. Design: This study was conducted using data from the Italian NINFEA birth cohort, which include children born between 2005 and 2016. Women who completed the 4-year NINFEA follow-up questionnaire before November 2020 (N = 5,307) were invited to complete a questionnaire targeted at evaluating the impacts of the pandemic on their children's health. The questionnaire asked mothers to report whether their children had a chronic disease or condition that required one or more regular health checks by a doctor in 2019 (used as a reference period) and whether the children had problems getting routine health checks after March 2020. Results: We obtained information on 3,721 children. Out of 353 children with a chronic disease that required at least one medical visit in 2019, 130 (36.8%) experienced problems during the pandemic. Lower family income was associated with a higher risk of experiencing health access problems. We observed that children living in families at lower income tertiles had more chance of experiencing healthcare access problems than children living in families at the highest income tertiles (prevalence rate ratio for a tertile decrease in family income: 1.22; 95% CIs: 1.02-1.49). Conclusion: Our study underlines that the COVID-19 pandemic may have caused healthcare access problems for children with prevalent chronic diseases, especially among those living in households with a low socioeconomic position.

Definitions of non-response and response to biological therapy for severe asthma: a systematic review.

Background: Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma. Methods: We searched four bibliographic databases from inception to 15 March 2021. Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken. Results: 13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated "very low" to "low" for quality of measurement properties and none met all quality standards. Conclusions: This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.

Long-term cardiometabolic health in people born after assisted reproductive technology: a multi-cohort analysis.

AIMS: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age. METHODS AND RESULTS: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant. CONCLUSION: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease.

Identifying and appraising outcome measures for severe asthma: a systematic review.

BACKGROUND: Valid outcome measures are imperative to evaluate treatment response, yet the suitability of existing end-points for severe asthma is unclear. This review aimed to identify outcome measures for severe asthma and appraise the quality of their measurement properties. METHODS: A literature search was performed to identify "candidate" outcome measures published between 2018 and 2020. A modified Delphi exercise was conducted to select "key" outcome measures within healthcare professional, patient, pharmaceutical and regulatory stakeholder groups. Initial validation studies for "key" measures were rated against modified quality criteria from COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). The evidence was discussed at multi-stakeholder meetings to ratify "priority" outcome measures. Subsequently, four bibliographic databases were searched from inception to 20 July 2020 to identify development and validation studies for these end-points. Two reviewers screened records, extracted data, assessed their methodological quality and graded the evidence according to COSMIN. RESULTS: 96 outcome measures were identified as "candidates", 55 as "key" and 24 as "priority" for severe asthma, including clinical, healthcare utilisation, quality of life, asthma control and composite. 32 studies reported measurement properties of 17 "priority" end-points from the latter three domains. Only the Severe Asthma Questionnaire and Childhood Asthma Control Test were developed with input from severe asthma patients. The certainty of evidence was "low" to "very low" for most "priority" end-points across all measurement properties and none fulfilled all quality standards. CONCLUSIONS: Only two outcome measures had robust developmental data for severe asthma. This review informed development of core outcome measures sets for severe asthma.

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA).

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

Unintentional injuries and potential determinants of falls in young children: Results from the Piccolipiù Italian birth cohort.

OBJECTIVES: Unintentional injuries such as falls, are particularly frequent in early childhood. To date, epidemiological studies in this field have been carried out using routine data sources or registries and many studies were observational studies with a cross-sectional design. The aims of the study are to describe unintentional injuries in the first two years of life in the Piccolipiù birth cohort, and to investigate the association between mother and children characteristics and the First Event of Raised surface Fall (FERF). METHODS: This longitudinal observational study included 3038 children from an Italian birth cohort. Data on socio-demographic factors, socio-economic indicators, maternal health and lifestyle characteristics and child's sleeping behavior, obtained from questionnaires completed at birth, 12 and 24 months of age, were considered in the analyses as potential risk factors of FERF. Time of occurrence of FERF was analyzed using the Kaplan-Meier method. The multivariable analysis for time to event was carried out using a Cox proportional hazards model. RESULTS: Falls from raised surfaces are the leading cause of unintentional injuries in the cohort with 610 (21.1%) and 577 (20.0%) cases among children during the first and second year of life, respectively. An increased risk of FERF was associated with several risk factors: maternal psychological distress (HR 1.41, 95%CI 1.10-1.81), maternal alcohol intake (HR 1.26, 95%CI 1.10-1.45), and child's sleeping problems (HR 1.28, 95%CI 1.09-1.51). Children with older aged mothers (HR 0.98, 95%CI 0.96-0.99) and living in northern Italy (HR 0.64, 95%CI 0.55-0.75) had a lower risk of FERF. CONCLUSION: The results of the study suggest that a higher risk of FERF is associated with socio-demographic factors, maternal characteristics and child sleeping behavior that could hinder parent empowerment.

Pregnancy outcomes in Italy during COVID-19 pandemic: a population-based cohort study.

OBJECTIVE: To compare the estimates of preterm birth (PTB; 22-36 weeks gestational age, GA) and stillbirth rates during COVID-19 pandemic in Italy with those recorded in the three previous years. DESIGN: A population-based cohort study of liveborn and stillborn infants was conducted using data from Regional Health Systems and comparing the pandemic period (March 1st , 2020-March 31st , 2021, N= 362,129) to an historical period (January 2017- February 2020, N=1,117,172). The cohort covered 84.3% of the births in Italy. METHODS: Poisson regressions were run in each Region and meta-analyses were performed centrally. We used an interrupted time series regression analysis to study the trend of preterm births from 2017 to 2021. MAIN OUTCOME MEASURES: The primary outcomes were PTB and stillbirths. Secondary outcomes were late PTB (32-36 weeks' GA), very PTB (<32 weeks' GA), and extremely PTB (<28 weeks' GA), overall and stratified into singleton and multiples. RESULTS: The pandemic period compared with the historical one was associated with a reduced risk for PTB (Risk Ratio: 0.91; 95% Confidence Interval, CI: 0.88, 0.93), late PTB (0.91; 0.88, 0.94), very PTB (0.88; 0.84, 0.91), and extremely PTB (0.88; 0.82, 0.95). In multiples, point estimates were not very different, but had wider CIs. No association was found for stillbirths (1.01; 0.90, 1.13). A linear decreasing trend in PTB rate was present in the historical period, with a further reduction after the lockdown. CONCLUSIONS: We demonstrated a decrease in PTB rate after the introduction of COVID-19 restriction measures, without an increase in stillbirths.

Delayed Start of Routine Vaccination in Preterm and Small-for-Gestational-Age Infants: An Area-Based Cohort Study from the Tuscany Region, Italy.

Preterm and small-for-gestational-age (SGA) infants are more susceptible to vaccine-preventable diseases. To evaluate routine vaccination timeliness in these high-risk groups, a full birth cohort of infants (n = 41,502) born in 2017 and 2018 in Tuscany was retrospectively followed up until 24 months of age. Infants were classified by gestational age (GA) and SGA status. The vaccinations included: hexavalent (HEXA), measles-mumps-rubella, varicella, pneumococcal conjugate (PCV), and meningococcal C conjugate. Time-to-event (Kaplan-Meier) analyses were conducted to evaluate the timing of vaccination according to GA; logistic models were performed to evaluate the associations between GA and SGA with vaccination timeliness. Time-to-event analyses show that the rate of delayed vaccine receipt increased with decreasing GA for all the vaccinations, with a less marked gradient in later vaccine doses. Compared to full-term infants, very preterm infants significantly showed an increased odds ratio (OR) for delayed vaccination in all the vaccinations, while moderate/late preterm infants only showed an increased OR for HEXA-1, HEXA-3, PCV-1, and PCV-3. SGA infants had a significantly higher risk of delayed vaccination only for HEXA-1 and PCV-1 compared to non-SGA infants. In conclusion, vaccinations among preterm and SGA infants showed considerable delay. Tailored public health programs to improve vaccination timeliness are required in these high-risk groups.

Early factors associated with risk of developmental coordination disorder in very preterm children: A prospective area-based cohort study in Italy.

BACKGROUND: Developmental coordination disorder (DCD) is a motor disorder of unknown aetiology that may have long-term consequences on daily activities, and psychological and physical health. Studies investigating risk factors for DCD have so far provided inconsistent results. OBJECTIVES: To assess, using a parent-report screening tool, risk of DCD in school-age very preterm children born in Italy, and investigate the associated early biomedical and sociodemographic factors. METHODS: A prospective area-based cohort (804 children, response rate 73.4%) was assessed at 8-11 years of age in three Italian regions. Perinatal data were abstracted from medical records. DCD risk was measured using the Italian-validated version of the Developmental Coordination Disorder Questionnaire (DCDQ-IT). For this study, children with cognitive deficit (i.e. intelligence quotient <70), cerebral palsy, severe vision and hearing disabilities, and other impairments affecting movement were excluded. A total of 629 children were analysed. We used inverse probability weighting to account for loss to follow-up, and multilevel, multivariable modified Poisson models to obtain adjusted risk ratio (aRR) and 95% confidence interval (CI). Missing values in the covariates were imputed. RESULTS: 195 children (weighted proportion 31.8%, 95% CI 28.2, 35.6) scored positive on the DCDQ-IT, corresponding to the 15th centile of the reference Movement-ABC test. Factors associated with overall DCD risk were male sex (aRR 1.35, 95% CI 1.05, 1.73), intrauterine growth restriction (aRR 1.45, 95% CI 1.14, 1.85), retinopathy of prematurity (aRR 1.62, 95% CI 1.07, 2.45), and older maternal age at delivery (aRR 1.39, 95% CI 1.09, 1.77). Complete maternal milk feeding at discharge from the neonatal unit and higher parental socio-economic status were associated with decreased risk. CONCLUSIONS: Both biomedical and sociodemographic factors increase DCD risk. These findings can contribute to elucidating the origins of this disorder, and assist in the identification of children at risk for early referral and intervention.

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.

Prenatal exposure to PM10 and changes in DNA methylation and telomere length in cord blood.

BACKGROUND: Air pollution exposure in pregnancy can cause molecular level alterations that might influence later disease susceptibility. OBJECTIVES: We investigated DNA methylation (DNAm) and telomere length (TL) in the cord blood in relation to gestational PM10 exposure and explored potential gestational windows of susceptibility. METHODS: Cord blood epigenome-wide DNAm (N = 384) and TL (N = 500) were measured in children of the Italian birth cohort Piccolipiù, using the Infinium Methylation EPIC BeadChip and qPCR, respectively. PM10 daily exposure levels, based on maternal residential address, were estimated for different gestational periods using models based on satellite data. Epigenome-wide analysis to identify differentially methylated probes (DMPs) and regions (DMRs) was conducted, followed by a pathway analysis and replication analysis in an second Piccolipiù dataset. Distributed lag models (DLMs) using weekly exposures were used to study the association of PM10 exposure across pregnancy with telomere length, as well as with the DMPs that showed robust associations. RESULTS: Gestational PM10 exposure was associated with the DNA methylation of more than 250 unique DMPs, most of them identified in early gestation, and 1 DMR. Out of 151 DMPs available in the replication dataset, ten DMPs showed robust associations: eight were associated with exposure during early gestation and 2 with exposure during the whole pregnancy. These exposure windows were supported by the DLM analysis. The PM10 exposure between 15th and 20th gestational week seem to be associated with shorter telomeres at birth, while exposure between 24th and 29th was associated with longer telomeres. DISCUSSION: The early pregnancy period is a potential critical window during which PM10 exposure can influence cord blood DNA methylation. The results from the TL analysis were consistent with previous findings and merit further exploration in future studies. The study underlines the importance of considering gestational windows outside of the predefined trimesters that may not always overlap with biologically relevant windows of exposure.

Lung function at school age in infants with lower respiratory tract infections with and without wheezing: A birth cohort study.

OBJECTIVE: To evaluate the relationship between lower respiratory tract infections (LRTI), in the first 2 years of life and lung function at school age in the Piccolipiù birth cohort (Italy). METHODS: Data on LRTI (doctor diagnosis of bronchitis, bronchiolitis, pneumonia) and wheezing (≥3 episodes or a diagnosis of asthmatic bronchitis) in the first 2 years of life were obtained from parental questionnaires. Lung function was assessed at 7 years by spirometry and forced volume vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, forced expiratory flow between 25% and 75%, and at 75% of FVC (FEF25-75 and FEF75 ) were reported as Z-scores. The associations between LRTI and spirometric variables were estimated with linear regression models. RESULTS: Among 877 children studied, 22.1% had LRTI only, 5.4% wheezing only, 13.2% had both, and 59.3% had neither LRTI nor wheezing. Children with LRTI had lower FVC and FEV1 than children without (Z-score differences: -0.18 [95% confidence intervals: -0.31; -0.06] and -0.15 [-0.27; -0.03]). When children were stratified by history of both LRTI and wheezing, there was no association between LRTI only and spirometric values. Conversely, having had both LRTI and wheezing was inversely associated with all lung function measures: Z-score differences of -0.24 (-0.42; -0.07); -0.42 (-0.59; -0.24); -0.25 (-0.41; -0.08); -0.37 (-0.54; -0.21); -0.30 (-0.46; -0.14) for FVC, FEV1, FEV1 /FVC, FEF25-75 and FEF75, respectively. CONCLUSION: Infants with wheezing and LRTI, but not those with LRTI only, had reduced lung function at school-age.

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.